Sample records for human fetal heart

  1. Myocardial bridges of the coronary arteries in the human fetal heart.

    PubMed

    Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

    2010-09-01

    During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

  2. Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

    NASA Technical Reports Server (NTRS)

    Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

    1996-01-01

    An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

  3. Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

    NASA Technical Reports Server (NTRS)

    Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, Robert A., III (Inventor)

    1994-01-01

    An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate is presented. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

  4. Cardioprotective stress response in the human fetal heart.

    PubMed

    Coles, John G; Boscarino, Cathy; Takahashi, Mark; Grant, Diane; Chang, Astra; Ritter, Julia; Dai, Xiaojing; Du, Changqing; Musso, Gabriel; Yamabi, Hideaki; Goncalves, Jason; Kumar, Ashu Sunny; Woodgett, James; Lu, Huanzhang; Hannigan, Gregory

    2005-05-01

    We propose that the fetal heart is highly resilient to hypoxic stress. Our objective was to elucidate the human fetal gene expression profile in response to simulated ischemia and reperfusion to identify molecular targets that account for the innate cardioprotection exhibited by the fetal phenotype. Primary cultures of human fetal cardiac myocytes (gestational age, 15-20 weeks) were exposed to simulated ischemia and reperfusion in vitro by using a simulated ischemic buffer under anoxic conditions. Total RNA from treated and baseline cells were isolated, reverse transcribed, and labeled with Cy3 or Cy5 and hybridized to a human cDNA microarray for expression analysis. This analysis revealed a highly significant (false discovery rate, <3%) suppression of interleukin 6 transcript levels during the reperfusion phase confirmed by means of quantitative polymerase chain reaction (0.25 +/- 0.11-fold). Interleukin 6 signaling during ischemia and reperfusion was assessed at the protein expression level by means of Western measurements of interleukin 6 receptor, the signaling subunit of the interleukin 6 receptor complex (gp130), and signal transducer of activated transcription 3. Posttranslational changes in the protein kinase B signaling pathway were determined on the basis of the phosphorylation status of protein kinase B, mitogen-activated protein kinase, and glycogen synthase kinase 3beta. The effect of suppression of a prohypertrophic kinase, integrin-linked kinase, with short-interfering RNA was determined in an ischemia and reperfusion-stressed neonatal rat cardiac myocyte model. Endogenous secretion of interleukin 6 protein in culture supernatants was measured by enzyme-linked immunosorbent assay. Human fetal cardiac myocytes exhibited a significantly lower rate of apoptosis induction during ischemia and reperfusion and after exposure to staurosporine and recombinant interleukin 6 compared with that observed in neonatal rat cardiac myocytes ( P < .05 for all

  5. Microarray Analysis of Differential Gene Expression Profile Between Human Fetal and Adult Heart.

    PubMed

    Geng, Zhimin; Wang, Jue; Pan, Lulu; Li, Ming; Zhang, Jitai; Cai, Xueli; Chu, Maoping

    2017-04-01

    Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes. Ten mRNAs were confirmed by quantificational real-time polymerase chain reaction. 5547 mRNAs were found to be significantly differentially expressed. "Cell cycle" was the most enriched pathway in the down-regulated genes. EFGR, IGF1R, and ITGB1 play a central role in the regulation of heart development. EGFR, IGF1R, and FGFR2 were the core genes regulating cardiac cell proliferation. The quantificational real-time polymerase chain reaction results were concordant with the microarray data. Our data identified the transcriptional regulation of heart development in the second trimester and the potential regulators that play a prominent role in the regulation of heart development and cardiac cells proliferation.

  6. A fetal human heart cardiac-inducing RNA (CIR) promotes the differentiation of stem cells into cardiomyocytes.

    PubMed

    Kochegarov, Andrei; Moses-Arms, Ashley; Lemanski, Larry F

    2015-08-01

    A specific human fetal heart RNA has been discovered, which has the ability to induce myocardial cell formation from mouse embryonic and human-induced pluripotent stem cells in culture. In this study, commercially obtained RNA from human fetal heart was cloned, sequenced, and synthesized using standard laboratory approaches. Molecular analyses of the specific fetal cardiac-inducing RNA (CIR), revealed that it is a fragment of N-sulfoglucosaminesulfohydrolase and the caspase recruitment domain family member 14 precursor. Stem cells transfected with CIRs often form into spindle-shaped cells characteristic of cardiomyocytes,and express the cardiac-specific contractile protein marker, troponin-T, in addition to tropomyosin and α-actinin as detected by immunohistochemical staining. Expression of these contractile proteins showed organization into sarcomeric myofibrils characteristic of striated cardiac muscle cells. Computer analyses of the RNA secondary structures of the active CIR show significant similarities to a RNA from salamander or myofibril-inducing RNA (MIR), which also promotes non-muscle cells to differentiate into cardiac muscle. Thus, these two RNAs, salamander MIR and the newly discovered human-cloned CIR reported here, appear to have evolutionarily conserved secondary structures suggesting that both play major roles in vertebrate heart development and, particularly, in the differentiation of cardiomyocytes from non-muscle cells during development.

  7. Passive Fetal Heart Monitoring System

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J. (Inventor); Mowrey, Dennis L. (Inventor)

    2003-01-01

    A fetal heart monitoring system and method for detecting and processing acoustic fetal heart signals transmitted by different signal transmission modes. One signal transmission mode, the direct contact mode, occurs in a first frequency band when the fetus is in direct contact with the maternal abdominal wall. Another signal transmission mode, the fluid propagation mode, occurs in a second frequency band when the fetus is in a recessed position with no direct contact with the maternal abdominal wall. The second frequency band is relatively higher than the first frequency band. The fetal heart monitoring system and method detect and process acoustic fetal heart signals that are in the first frequency band and in the second frequency band.

  8. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts.

    PubMed

    Schultz, Francisca; Hasan, Alveera; Alvarez-Laviada, Anita; Miragoli, Michele; Bhogal, Navneet; Wells, Sarah; Poulet, Claire; Chambers, Jenny; Williamson, Catherine; Gorelik, Julia

    2016-01-01

    Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts. Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential. We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells. UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts

  9. Fetal Echocardiography/Your Unborn Baby's Heart

    MedlinePlus

    ... heart for the doctor to evaluate. The sound waves can also detect blood flow throughout the baby's heart. This enables the doctor to evaluate the structure and function of the fetal heart. Who needs one? Fetal ...

  10. Fetal heart rate monitoring.

    PubMed

    Nageotte, Michael P

    2015-06-01

    Electronic fetal heart rate monitoring is a widely utilized means of assessment of fetal status during labor. Whereas little evidence exists regarding efficacy, this modality continues to be used extensively in every modern labor and delivery unit in developed countries. It is of importance that all providers of health care to the woman in labor and her newborn have a clear understanding of the basic pathophysiology of fetal heart rate monitoring and an appreciation for labor course and concerns as they arise in order to optimize outcomes and patient safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Early Evaluation of the Fetal Heart.

    PubMed

    Hernandez-Andrade, Edgar; Patwardhan, Manasi; Cruz-Lemini, Mónica; Luewan, Suchaya

    2017-01-01

    Evaluation of the fetal heart at 11-13 + 6 weeks of gestation is indicated for women with a family history of congenital heart defects (CHD), a previous child with CDH, or an ultrasound finding associated with cardiac anomalies. The accuracy for early detection of CHD is highly related to the experience of the operator. The 4-chamber view and outflow tracts are the most important planes for identification of an abnormal heart, and can be obtained in the majority of fetuses from 11 weeks of gestation onward. Transvaginal ultrasound is the preferred route for fetal cardiac examination prior to 12 weeks of gestation, whereas, after 12 weeks, the fetal heart can be reliably evaluated by transabdominal ultrasound. Cardiac defects, such as ventricular septal defects, tetralogy of Fallot, Ebstein's anomaly, or cardiac tumors, are unlikely to be identified at ≤14 weeks of gestation. Additional ultrasound techniques such as spatiotemporal image correlation and the evaluation of volumes by a fetal-heart expert can improve the detection of congenital heart disease. The evaluation of the fetal cardiac function at 11-13 + 6 weeks of gestation can be useful for early identification of fetuses at risk of anemia due to hemoglobinopathies, such as hemoglobin Bart's disease. © 2017 S. Karger AG, Basel.

  12. Human Fetal Behavior: 100 Years of Study.

    ERIC Educational Resources Information Center

    Kisilevsky, B. S.; Low, J. A.

    1998-01-01

    Reviews literature on human fetal behavior. Includes descriptions of coupling of body movements and fetal heart rate and behavior maturation from conception to term. Discusses use of stimulus-induced behavior to examine sensory and cognitive development, and spontaneous and stimulus-induced behavior to assess fetal well-being. Notes research focus…

  13. Hypoxia and fetal heart development.

    PubMed

    Patterson, A J; Zhang, L

    2010-10-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

  14. Fetal heart rate and fetal heart rate variability in Lipizzaner broodmares.

    PubMed

    Baska-Vincze, Boglárka; Baska, Ferenc; Szenci, Ottó

    2015-03-01

    Monitoring fetal heart rate (FHR) and fetal heart rate variability (FHRV) helps to understand and evaluate normal and pathological conditions in the foal. The aim of this study was to establish normal heart rate reference values for the ongoing equine pregnancy and to perform a heart rate variability (HRV) time-domain analysis in Lipizzaner mares. Seventeen middle- and late-term (days 121-333) pregnant Lipizzaner mares were examined using fetomaternal electrocardiography (ECG). The mean FHR (P = 0.004) and the standard deviation of FHR (P = 0.012) significantly decreased during the pregnancy. FHR ± SD values decreased from 115 ± 35 to 79 ± 9 bpm between months 5 and 11. Our data showed that HRV in the foal decreased as the pregnancy progressed, which is in contrast with the findings of earlier equine studies. The standard deviation of normal-normal intervals (SDNN) was higher (70 ± 25 to 166 ± 108 msec) than described previously. The root mean square of successive differences (RMSSD) decreased from 105 ± 69 to 77 ± 37 msec between the 5th and 11th month of gestation. Using telemetric ECG equipment, we could detect equine fetal heartbeat on day 121 for the first time. In addition, the large differences observed in the HR values of four mare-fetus pairs in four consecutive months support the assumption that there might be 'high-HR' and 'low-HR' fetuses in horses. It can be concluded that the analysis of FHR and FHRV is a promising tool for the assessment of fetal well-being but the applicability of these parameters in the clinical setting and in studs requires further investigation.

  15. Correlation of fetal oxygen saturation to fetal heart rate patterns. Evaluation of fetal pulse oximetry with two different oxisensors.

    PubMed

    Luttkus, A K; Friedmann, W; Homm-Luttkus, C; Dudenhausen, J W

    1998-03-01

    The purpose of this study was the correlation of fetal oxygen saturation values to various fetal heart rate patterns, as well as to oxygen saturation values obtained by fetal blood analysis. These objectives need to be evaluated from the perspective that two generations of fetal oxisensors have been used. Two different oxisensor systems (FS10: 660+890 nm and FS14: 735+890 nm) and a blinded pulse oximeter (type N400, Nellcor Puritan Bennett) were utilized to monitor 112 fetuses. All data, including oxygen saturation, fetal heart rate patterns, signal and contact quality were stored on a personal computer and evaluated after delivery. The following median fetal oxygen saturation values were obtained: during reassuring fetal heart rate sequences 54% with the oxisensor FS10 and 48% with the newer FS14 oxisensor, during intervals of variable decelerations 43% with the FS10 oxisensor and 40% with the FS14 oxisensor. These differences between values obtained during normal and abnormal fetal heart rate patterns are significant. Due to non-reassuring fetal heart rate patterns 81 fetal blood analyses were performed. The values of pulse oximetry were 9% higher (6% for the FS14) than those of spectrophotometry. Correlation of both methods was r=0.66 (0.74 for the FS14). In combination with fetal heart rate monitoring, fetal pulse oximetry promises a better differentiation between low and high risk heart rate patterns. Oxygen saturation values from intermittent fetal blood sampling reassure the clinician concerning the accuracy of this new method of intrapartum fetal surveillance and underline the increased quality of the new generation of oxisensor using light of a wavelength of 735 and 890 nm.

  16. Passive Fetal Heart Monitoring System

    NASA Technical Reports Server (NTRS)

    Bryant, Timothy D. (Inventor); Wynkoop, Mark W. (Inventor); Holloway, Nancy M. H. (Inventor); Zuckerwar, Allan J. (Inventor)

    2004-01-01

    A fetal heart monitoring system preferably comprising a backing plate having a generally concave front surface and a generally convex back surface, and at least one sensor element attached to the concave front surface for acquiring acoustic fetal heart signals produced by a fetus within a body. The sensor element has a shape that conforms to the generally concave back surface of the backing plate. In one embodiment, the at least one sensor element comprises an inner sensor, and a plurality of outer sensors surrounding the inner sensor. The fetal heart monitoring system can further comprise a web belt, and a web belt guide movably attached to the web belt. The web belt guide being is to the convex back surface of the backing plate.

  17. Antenatal fetal heart rate and "maternal intuition" as predictors of fetal sex.

    PubMed

    Genuis, S; Genuis, S K; Chang, W C

    1996-06-01

    To determine if the antenatal fetal heart rate is a reliable predictor of fetal sex, if there is any correlation between "maternal intuition" and fetal gender, and if maternal intuition favors one sex over the other. Two hundred twelve consecutive maternity patients with singleton gestations underwent a total of 2,261 antepartum visits. Fetal heart rate assessment was carried out between 14 and 41 weeks of gestation. At 32 weeks, participants were asked if they had a strong intuitive feeling regarding the fetal gender. Following birth, data on the infant were recorded, and the information was analyzed. There was no significant difference in the baseline fetal heart rate between male and female fetuses at any recorded gestational age. One hundred ten patients (51.9%) in the sample indicated a strong belief about the sex of their fetuses, with the majority (63.6%) predicting a male. The accuracy of maternal intuition, however, was not significantly different from that of random guessing. In the current era of declining family size, an increased focus on absolute reproductive choice and proliferating reproductive technological services, prenatal sex determination and sex selection will continue to provoke increasing attention. Fetal heart rate determination and maternal intuition, however, are not valid predictors of fetal gender.

  18. Fetal heart and uterine contraction monitor (image)

    MedlinePlus

    The fetal heart monitor and uterine contraction monitor provide a continuous record of the baby's heart rate and the mother's contraction rate as labor progresses. This device can provide early warning of fetal distress.

  19. Assessment of the concordance among 2-tier, 3-tier, and 5-tier fetal heart rate classification systems.

    PubMed

    Gyamfi Bannerman, Cynthia; Grobman, William A; Antoniewicz, Leah; Hutchinson, Maria; Blackwell, Sean

    2011-09-01

    In 2008, a National Institute of Child Health and Human Development/Society for Maternal-Fetal Medicine-sponsored workshop on electronic fetal monitoring recommended a new fetal heart tracing interpretation system. Comparison of this 3-tier system with other systems is lacking. Our purpose was to determine the relationships between fetal heart rate categories for the 3 existing systems. Three Maternal-Fetal Medicine specialists reviewed 120 fetal heart rates. All tracings were from term, singleton pregnancies with known umbilical artery pH. The fetal heart rates were classified by a 2-tier, 3-tier, and 5-tier system. Each Maternal-Fetal Medicine examiner reviewed 120 fetal heart rate segments. When compared with the 2-tier system, 0%, 54%, and 100% tracings in categories 1, 2, and 3 were "nonreassuring." There was strong concordance between category 1 and "green" as well as category 3 and "red" tracings. The 3-tier and 5-tier systems were similar in fetal heart rate interpretations for tracings that were either very normal or very abnormal. Whether one system is superior to the others in predicting fetal acidemia remains unknown. Copyright © 2011 Mosby, Inc. All rights reserved.

  20. The influence of betamethasone on fetal heart rate variability, obtained by non-invasive fetal electrocardiogram recordings.

    PubMed

    Verdurmen, Kim M J; Warmerdam, Guy J J; Lempersz, Carlijn; Hulsenboom, Alexandra D J; Renckens, Joris; Dieleman, Jeanne P; Vullings, Rik; van Laar, Judith O E H; Oei, S Guid

    2018-04-01

    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. To describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings. Prospective cohort study. Patients that require betamethasone, with a gestational age from 24 weeks onwards. Fetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement. 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. 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. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Effect of tocolytic drugs on fetal heart rate variability: a systematic review.

    PubMed

    Verdurmen, Kim M J; Hulsenboom, Alexandra D J; van Laar, Judith O E H; Oei, S Guid

    2017-10-01

    Tocolytics may cause changes in fetal heart rate (HR) pattern, while fetal heart rate variability (HRV) is an important marker of fetal well-being. We aim to systematically review the literature on how tocolytic drugs affect fetal HRV. We searched CENTRAL, PubMed and EMBASE up to June 2016. Studies published in English, using computerized or visual analysis to describe the effect of tocolytics on HRV in human fetuses were included. Studies describing tocolytics during labor, external cephalic version, pre-eclampsia and infection were excluded. Eventually, we included six studies, describing 169 pregnant women. Nifedipine, atosiban and indomethacin administration show no clinically important effect on fetal HRV. Following administration of magnesium sulfate decreased variability and cases of bradycardia are described. Fenoterol administration results in a slight increase in fetal HR with no changes in variability. After ritodrine administration increased fetal HR and decreased variability is seen. The effect of co-administration of corticosteroids should be taken into account. In order to prevent iatrogenic preterm labor, the effects of tocolytic drugs on fetal HRV should be taken into account when monitoring these fetuses.

  2. Influence of ECG sampling rate in fetal heart rate variability analysis.

    PubMed

    De Jonckheere, J; Garabedian, C; Charlier, P; Champion, C; Servan-Schreiber, E; Storme, L; Debarge, V; Jeanne, M; Logier, R

    2017-07-01

    Fetal hypoxia results in a fetal blood acidosis (pH<;7.10). In such a situation, the fetus develops several adaptation mechanisms regulated by the autonomic nervous system. Many studies demonstrated significant changes in heart rate variability in hypoxic fetuses. So, fetal heart rate variability analysis could be of precious help for fetal hypoxia prediction. Commonly used fetal heart rate variability analysis methods have been shown to be sensitive to the ECG signal sampling rate. Indeed, a low sampling rate could induce variability in the heart beat detection which will alter the heart rate variability estimation. In this paper, we introduce an original fetal heart rate variability analysis method. We hypothesize that this method will be less sensitive to ECG sampling frequency changes than common heart rate variability analysis methods. We then compared the results of this new heart rate variability analysis method with two different sampling frequencies (250-1000 Hz).

  3. Prenatal diagnosis of congenital fetal heart abnormalities and clinical analysis.

    PubMed

    Li, Hui; Wei, Jun; Ma, Ying; Shang, Tao

    2005-09-01

    To study the value of detecting fetal congenital heart disease (CHD) using the five transverse planes technique of fetal echocardiography. Nine hundred and eighty-two high-risk pregnancies for fetal CHD were included in this study, the fetal heart was scanned with the five transverse planes technique of fetal echocardiography described by Yagel, autopsy was conducted when pregnancy was terminated. Blood from fetal heart was collected for fetal chromosome analysis. A close follow-up was given for normal fetal heart pregnancies and neonatal echocardiography was performed to check the accuracy of prenatal diagnosis. (1) Forty-six cases (4.68%) were found to have fetal heart abnormalities in this study, 69.56% of them were diagnosed by single four-chamber view, another 30.43% fetal CHD were found by combining other views; (2) Forty-one parents of prenatal fetuses with CHD chose to terminate pregnancy, thirty-two of them gave consent to conduct autopsy, 93.75% of which yielded unanimous conclusion between prenatal fetal echocardiography and autopsy; (3) Thirty-two of 46 cases underwent fetal chromosome analysis, 8 cases (25%) were found to have abnormal chromosome; (4) Five cases were found to have right ventricle and atrium a little bigger than those on the left side, with the unequal condition being the same after birth, but there were no clinical manifestations and they are healthy for the time being; (5) Nine hundred and thirty-six cases were not found with abnormality in this study, but one case was diagnosed with ventricular septal defect after birth, one case was diagnosed with patent ductus arteriosus, one case had atrial septal defect after birth. (1) The detected CHD rate was 4.68% by screening fetal heart with five transverse planes according to Yagel's description of high risk population basis for CHD. The coinciding rate of prenatal diagnosis and autopsy was 93.75%; (2) The sensitivity of detecting fetal heart abnormality is 92%, the specificity is 99

  4. Ultrasound transducer positioning aid for fetal heart rate monitoring.

    PubMed

    Hamelmann, Paul; Kolen, Alex; Schmitt, Lars; Vullings, Rik; van Assen, Hans; Mischi, Massimo; Demi, Libertario; van Laar, Judith; Bergmans, Jan

    2016-08-01

    Fetal heart rate (fHR) monitoring is usually performed by Doppler ultrasound (US) techniques. For reliable fHR measurements it is required that the fetal heart is located within the US beam. In clinical practice, clinicians palpate the maternal abdomen to identify the fetal presentation and then the US transducer is fixated on the maternal abdomen where the best fHR signal can be obtained. Finding the optimal transducer position is done by listening to the strength of the Doppler audio output and relying on a signal quality indicator of the cardiotocographic (CTG) measurement system. Due to displacement of the US transducer or displacement of the fetal heart out of the US beam, the fHR signal may be lost. Therefore, it is often necessary that the obstetrician repeats the tedious procedure of US transducer positioning to avoid long periods of fHR signal loss. An intuitive US transducer positioning aid would be highly desirable to increase the work flow for the clinical staff. In this paper, the possibility to determine the fetal heart location with respect to the transducer by exploiting the received signal power in the transducer elements is shown. A commercially available US transducer used for fHR monitoring is connected to an US open platform, which allows individual driving of the elements and raw US data acquisition. Based on the power of the received Doppler signals in the transducer elements, the fetal heart location can be estimated. A beating fetal heart setup was designed and realized for validation. The experimental results show the feasibility of estimating the fetal heart location with the proposed method. This can be used to support clinicians in finding the optimal transducer position for fHR monitoring more easily.

  5. Maternal exercise, season and sex modify the daily fetal heart rate rhythm.

    PubMed

    Sletten, J; Cornelissen, G; Assmus, J; Kiserud, T; Albrechtsen, S; Kessler, J

    2018-05-13

    The knowledge on biological rhythms is rapidly expanding. We aimed to define the longitudinal development of the daily (24-hour) fetal heart rate rhythm in an unrestricted, out-of-hospital setting and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Daily rhythms in fetal heart rate and fetal heart rate variation were detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant daily rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (P < .001) and nonlinearly in males (quadratic function, P = .001). At 32 and 36 weeks, interindividual rhythm diversity was found in male fetuses during higher maternal physical activity and during the summer season. The dynamic development of the daily fetal heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Randomised controlled trial of intrapartum fetal heart rate monitoring.

    PubMed

    Mahomed, K; Nyoni, R; Mulambo, T; Kasule, J; Jacobus, E

    1994-02-19

    To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. Prospective randomised controlled trial. Referral maternity hospital, Harare, Zimbabwe. 1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight, two, five, and nine cases respectively. Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use of relatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.

  7. Interdisciplinary Team Huddles for Fetal Heart Rate Tracing Review.

    PubMed

    Thompson, Lisa; Krening, Cynthia; Parrett, Dolores

    2018-06-01

    To address an increase in unexpected poor outcomes in term neonates, our team developed a goal of high reliability and improved fetal safety in the culture of the Labor and Delivery nursing department. We implemented interdisciplinary reviews of fetal heart rate, along with a Category II fetal heart rate management algorithm and a fetal heart rate assessment rapid response alert to call for unscheduled reviews when needed. Enhanced communication between nurses and other clinicians supported an interdisciplinary approach to fetal safety, and we observed an improvement in health outcomes for term neonates. We share our experience with the intention of making our methods available to any labor and delivery unit team committed to safe, high-quality care and service excellence. Copyright © 2018 AWHONN. Published by Elsevier Inc. All rights reserved.

  8. Toward noninvasive monitoring of ongoing electrical activity of human uterus and fetal heart and brain.

    PubMed

    Lew, S; Hämäläinen, M S; Okada, Y

    2017-12-01

    To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs. A simulation study was carried out for a scanner with an array of magnetic field sensors placed all around the torso from the chest to the hip within a horizontal magnetic shielding enclosure. The magnetic fields from internal organs and an external noise source were computed for a pregnant woman with a 35-week old fetus. Signal processing methods were used to reject the external and internal interferences, to visualize uterine activity, and to detect activity of fetal heart and brain. External interference was reduced by a factor of 1000, sufficient for detecting signals from internal organs when combined with passive and active shielding. The scanner rejects internal interferences better than partial-coverage arrays. It can be used to estimate currents around the uterus. It clearly detects spontaneous activity from the fetal heart and brain without averaging and weaker evoked brain activity at all fetal head positions after averaging. The simulated device will be able to monitor the ongoing activity of the fetal and maternal organs. This type of scanner may become a novel tool in fetal medicine. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  9. Signal processing methodologies for an acoustic fetal heart rate monitor

    NASA Technical Reports Server (NTRS)

    Pretlow, Robert A., III; Stoughton, John W.

    1992-01-01

    Research and development is presented of real time signal processing methodologies for the detection of fetal heart tones within a noise-contaminated signal from a passive acoustic sensor. A linear predictor algorithm is utilized for detection of the heart tone event and additional processing derives heart rate. The linear predictor is adaptively 'trained' in a least mean square error sense on generic fetal heart tones recorded from patients. A real time monitor system is described which outputs to a strip chart recorder for plotting the time history of the fetal heart rate. The system is validated in the context of the fetal nonstress test. Comparisons are made with ultrasonic nonstress tests on a series of patients. Comparative data provides favorable indications of the feasibility of the acoustic monitor for clinical use.

  10. Randomised controlled trial of intrapartum fetal heart rate monitoring.

    PubMed Central

    Mahomed, K.; Nyoni, R.; Mulambo, T.; Kasule, J.; Jacobus, E.

    1994-01-01

    OBJECTIVE--To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. DESIGN--Prospective randomised controlled trial. SETTING--Referral maternity hospital, Harare, Zimbabwe. SUBJECTS--1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. INTERVENTIONS--Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. MAIN OUTCOME MEASURES--Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. RESULTS--Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight, two, five, and nine cases respectively. CONCLUSIONS--Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use of relatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources. PMID:8136665

  11. Prospective evaluation of the fetal heart using Fetal Intelligent Navigation Echocardiography (FINE).

    PubMed

    Garcia, M; Yeo, L; Romero, R; Haggerty, D; Giardina, I; Hassan, S S; Chaiworapongsa, T; Hernandez-Andrade, E

    2016-04-01

    To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in

  12. Monitoring the fetal heart rate variability during labor.

    PubMed

    Moslem, B; Mohydeen, A; Bazzi, O

    2015-08-01

    In respect to the main goal of our ongoing work for estimating the heart rate variability (HRV) from fetal electrocardiogram (FECG) signals for monitoring the health of the fetus, we investigate in this paper the possibility of extracting the fetal heart rate variability (HRV) directly from the abdominal composite recordings. Our proposed approach is based on a combination of two techniques: Periodic Component Analysis (PiCA) and recursive least square (RLS) adaptive filtering. The Fetal HRV of the estimated FECG signal is compared to a reference value extracted from an FECG signal recorded by using a spiral electrode attached directly to the fetal scalp. The results obtained show that the fetal HRV can be directly evaluated from the abdominal composite recordings without the need of recording an external reference signal.

  13. [Current status and recommendations for intrapartum monitoring of fetal heart rate].

    PubMed

    Měchurová, A; Velebil, P; Hruban, L; Janků, P

    2016-04-01

    Monitoring of fetal heart rate is one of the basic components of obstetrical care, in which the cardiotocography remains the gold standard and screening method in early diagnosis of fetal hypoxia, even after introduction of other selective methods of intrauterine monitoring of fetal well-being. The review article is divided into several parts: pathophysiology of fetal oxygenation, fetal heart rate and changes of fetal hemodynamics, and rules for fetal heart rate auscultation. The main principles of cardiotocographic monitoring and evaluation of ante- and intrapartrum recordings according to the FIGO criteria from 1986 and evaluation of intrapartum recordings according to the 2015 FIGO recommendations are mentioned. At the end a comparative table of 1986 FIGO and 2015 FIGO criteria is presented. Review.

  14. Effect of uterine contractions on fetal heart rate in pregnancy: a prospective observational study.

    PubMed

    Sletten, Julie; Kiserud, Torvid; Kessler, Jörg

    2016-10-01

    The new Holter monitoring technology enables long-term electrocardiographic recording of the fetal heart rate without discomfort for the mother. The aim of the study was to assess the feasibility of a fetal Holter monitor. This technology was further used to study fetal heart rate outside the hospital setting during normal daily activities and to test the hypothesis that uterine activity during pregnancy influences fetal heart rate. Prospective observational study including 12 healthy pregnant women at 20-40 weeks of gestation. Data were collected using the Monica AN24 system. Outcome measures were fetal heart rate, maternal heart rate, and uterine activity categorized according to the strength of the electrohysterographic signal. The recordings had a median length of 18.8 h, and fetal heart rate and maternal heart rate were obtained with success rates of 73.1 and 99.9%, respectively. Uterine activity was found to affect fetal heart rate in all participants. Compared with the basal tone and mild levels of uterine activity, moderate and strong levels of uterine activity were associated with increases in fetal heart rate of 4.0 and 5.7 beats/min, respectively. At night, the corresponding increases were 4.9 and 7.6 beats/min. Linear correlations were found between maternal heart rate and fetal heart rate in 11 of the 12 cases, with a mean coefficient beta of 0.189. Both maternal heart rate and fetal heart rate exhibited a diurnal pattern, with lower heart rates being recorded at night. Uterine activity during pregnancy is associated with a graded response in fetal heart rate and may represent a physiological challenge for the development and adaptation of the fetal cardiovascular system. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  15. Quantification of fetal heart rate regularity using symbolic dynamics

    NASA Astrophysics Data System (ADS)

    van Leeuwen, P.; Cysarz, D.; Lange, S.; Geue, D.; Groenemeyer, D.

    2007-03-01

    Fetal heart rate complexity was examined on the basis of RR interval time series obtained in the second and third trimester of pregnancy. In each fetal RR interval time series, short term beat-to-beat heart rate changes were coded in 8bit binary sequences. Redundancies of the 28 different binary patterns were reduced by two different procedures. The complexity of these sequences was quantified using the approximate entropy (ApEn), resulting in discrete ApEn values which were used for classifying the sequences into 17 pattern sets. Also, the sequences were grouped into 20 pattern classes with respect to identity after rotation or inversion of the binary value. There was a specific, nonuniform distribution of the sequences in the pattern sets and this differed from the distribution found in surrogate data. In the course of gestation, the number of sequences increased in seven pattern sets, decreased in four and remained unchanged in six. Sequences that occurred less often over time, both regular and irregular, were characterized by patterns reflecting frequent beat-to-beat reversals in heart rate. They were also predominant in the surrogate data, suggesting that these patterns are associated with stochastic heart beat trains. Sequences that occurred more frequently over time were relatively rare in the surrogate data. Some of these sequences had a high degree of regularity and corresponded to prolonged heart rate accelerations or decelerations which may be associated with directed fetal activity or movement or baroreflex activity. Application of the pattern classes revealed that those sequences with a high degree of irregularity correspond to heart rate patterns resulting from complex physiological activity such as fetal breathing movements. The results suggest that the development of the autonomic nervous system and the emergence of fetal behavioral states lead to increases in not only irregular but also regular heart rate patterns. Using symbolic dynamics to

  16. Small-volume amnioinfusion: a potential stimulus of intrapartum fetal heart rate accelerations.

    PubMed

    Wax, Joseph R; Flaherty, Nina; Pinette, Michael G; Blackstone, Jacquelyn; Cartin, Angelina

    2004-02-01

    We describe a recurrent nonreassuring fetal heart rate pattern in which small-volume amnioinfusions apparently evoked fetal heart rate accelerations suggested fetal well-being, allowing that progressive labor that culminated in the vaginal delivery of a healthy infant.

  17. Transfer entropy analysis of maternal and fetal heart rate coupling.

    PubMed

    Marzbanrad, Faezeh; Kimura, Yoshitaka; Endo, Miyuki; Palaniswami, Marimuthu; Khandoker, Ahsan H

    2015-01-01

    Although evidence of the short term relationship between maternal and fetal heart rates has been found in previous model-based studies, knowledge about the mechanism and patterns of the coupling during gestation is still limited. In this study, a model-free method based on Transfer Entropy (TE) was applied to quantify the maternal-fetal heart rate couplings in both directions. Furthermore, analysis of the lag at which TE was maximum and its changes throughout gestation, provided more information about the mechanism of coupling and its latency. Experimental results based on fetal electrocardiograms (fECGs) and maternal ECG showed the evidence of coupling for 62 out of 65 healthy mothers and fetuses in each direction, by statistically validating against the surrogate pairs. The fetuses were divided into three gestational age groups: early (16-25 weeks), mid (26-31 weeks) and late (32-41 weeks) gestation. The maximum TE from maternal to fetal heart rate significantly increased from early to mid gestation, while the coupling delay on both directions decreased significantly from mid to late gestation. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. In conclusion, the application of TE with delays revealed detailed information about the changes in fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.

  18. Fetal behavior and heart rate in twin pregnancy: a review.

    PubMed

    Tendais, Iva; Visser, Gerard H A; Figueiredo, Bárbara; Montenegro, Nuno; Mulder, Eduard J H

    2013-04-01

    Fetal movements and fetal heart rate (FHR) are well-established markers of fetal well-being and maturation of the fetal central nervous system. The purpose of this paper is to review and discuss the available knowledge on fetal movements and heart rate patterns in twin pregnancies. There is some evidence for an association or similarity in fetal movement incidences or FHR patterns between both members of twin pairs. However, the temporal occurrence of these patterns seems to be for the most part asynchronous, especially when stricter criteria are used to define synchrony. The available data suggest that fetal behavior is largely independent of sex combination, fetal position, and presentation. Conversely, chorionicity appears to have some influence on fetal behavior, mainly before 30 weeks of gestation. There is preliminary evidence for the continuity of inter-individual differences in fetal activity and FHR patterns over pregnancy. Comparisons between studies are limited by large methodological differences and absence of uniform concepts and definitions. Future studies with high methodological quality are needed to provide a more comprehensive knowledge of normal fetal behavior in twin pregnancy.

  19. Improved ultrasound transducer positioning by fetal heart location estimation during Doppler based heart rate measurements.

    PubMed

    Hamelmann, Paul; Vullings, Rik; Schmitt, Lars; Kolen, Alexander F; Mischi, Massimo; van Laar, Judith O E H; Bergmans, Jan W M

    2017-09-21

    Doppler ultrasound (US) is the most commonly applied method to measure the fetal heart rate (fHR). When the fetal heart is not properly located within the ultrasonic beam, fHR measurements often fail. As a consequence, clinical staff need to reposition the US transducer on the maternal abdomen, which can be a time consuming and tedious task. In this article, a method is presented to aid clinicians with the positioning of the US transducer to produce robust fHR measurements. A maximum likelihood estimation (MLE) algorithm is developed, which provides information on fetal heart location using the power of the Doppler signals received in the individual elements of a standard US transducer for fHR recordings. The performance of the algorithm is evaluated with simulations and in vitro experiments performed on a beating-heart setup. Both the experiments and the simulations show that the heart location can be accurately determined with an error of less than 7 mm within the measurement volume of the employed US transducer. The results show that the developed algorithm can be used to provide accurate feedback on fetal heart location for improved positioning of the US transducer, which may lead to improved measurements of the fHR.

  20. A genome resource to address mechanisms of developmental programming: determination of the fetal sheep heart transcriptome.

    PubMed

    Cox, Laura A; Glenn, Jeremy P; Spradling, Kimberly D; Nijland, Mark J; Garcia, Roy; Nathanielsz, Peter W; Ford, Stephen P

    2012-06-15

    The pregnant sheep has provided seminal insights into reproduction related to animal and human development (ovarian function, fertility, implantation, fetal growth, parturition and lactation). Fetal sheep physiology has been extensively studied since 1950, contributing significantly to the basis for our understanding of many aspects of fetal development and behaviour that remain in use in clinical practice today. Understanding mechanisms requires the combination of systems approaches uniquely available in fetal sheep with the power of genomic studies. Absence of the full range of sheep genomic resources has limited the full realization of the power of this model, impeding progress in emerging areas of pregnancy biology such as developmental programming. We have examined the expressed fetal sheep heart transcriptome using high-throughput sequencing technologies. In so doing we identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. Genes with the highest expression levels and with novel exons in the fetal heart transcriptome are known to play central roles in muscle development. We show that high-throughput sequencing methods can generate extensive transcriptome information in the absence of an assembled and annotated genome for that species. The gene sequence data obtained provide a unique genomic resource for sheep specific genetic technology development and, combined with the polymorphism data, augment annotation and assembly of the sheep genome. In addition, identification and pathway analysis of novel fetal sheep heart transcriptome splice variants is a first step towards revealing mechanisms of genetic variation and gene environment interactions during fetal heart development.

  1. A genome resource to address mechanisms of developmental programming: determination of the fetal sheep heart transcriptome

    PubMed Central

    Cox, Laura A; Glenn, Jeremy P; Spradling, Kimberly D; Nijland, Mark J; Garcia, Roy; Nathanielsz, Peter W; Ford, Stephen P

    2012-01-01

    The pregnant sheep has provided seminal insights into reproduction related to animal and human development (ovarian function, fertility, implantation, fetal growth, parturition and lactation). Fetal sheep physiology has been extensively studied since 1950, contributing significantly to the basis for our understanding of many aspects of fetal development and behaviour that remain in use in clinical practice today. Understanding mechanisms requires the combination of systems approaches uniquely available in fetal sheep with the power of genomic studies. Absence of the full range of sheep genomic resources has limited the full realization of the power of this model, impeding progress in emerging areas of pregnancy biology such as developmental programming. We have examined the expressed fetal sheep heart transcriptome using high-throughput sequencing technologies. In so doing we identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. Genes with the highest expression levels and with novel exons in the fetal heart transcriptome are known to play central roles in muscle development. We show that high-throughput sequencing methods can generate extensive transcriptome information in the absence of an assembled and annotated genome for that species. The gene sequence data obtained provide a unique genomic resource for sheep specific genetic technology development and, combined with the polymorphism data, augment annotation and assembly of the sheep genome. In addition, identification and pathway analysis of novel fetal sheep heart transcriptome splice variants is a first step towards revealing mechanisms of genetic variation and gene environment interactions during fetal heart development. PMID:22508961

  2. THE EFFECTS OF SPINAL ANESTHESIA ON THE FETAL HEART RATE

    PubMed Central

    Downs, Howard S.; Morrison, Philip H.

    1963-01-01

    The effect of spinal anesthesia on fetal heart rate is due to maternal hypotension and subsequent fetal hypoxia. Maternal hypotension of 80 mm of mercury for five minutes almost always results in hypoxic fetal bradycardia. This bradycardia is gradual in onset, and may be preceded by a short period of fetal tachycardia. There is a lag in the return of fetal heart rate to normal after maternal blood pressure has normalized. Similar bradycardia has been observed in maternal syncope unassociated with anesthesia. Maternal hypotension should be prevented, and if it occurs should be corrected early. Administration of a vasopressor drug is the treatment of choice, with oxygen and fluids as indicated. ImagesFigure 1.Figure 3.Figure 4.Figure 5. PMID:14084683

  3. A systematic review of prenatal screening for congenital heart disease by fetal electrocardiography.

    PubMed

    Verdurmen, Kim M J; Eijsvoogel, Noortje B; Lempersz, Carlijn; Vullings, Rik; Schroer, Christian; van Laar, Judith O E H; Oei, S Guid

    2016-11-01

    Congenital heart disease (CHD) is the most common severe congenital anomaly worldwide. Diagnosis early in pregnancy is important, but the detection rate by two-dimensional ultrasonography is only 65%-81%. To evaluate existing data on CHD and noninvasive abdominal fetal electrocardiography (ECG). A systematic review was performed through a search of the Cochrane Library, PubMed, and Embase for studies published up to April 2016 using the terms "congenital heart disease," "fetal electrocardiogram," and other similar keywords. Primary articles that described changes in fetal ECG among fetuses with CHD published in English were included. Outcomes of interest were changes in fetal ECG parameters observed for fetuses with congenital heart disease. Findings were reported descriptively. Only five studies described changes observed in the fetal electrocardiogram for fetuses with CHD, including heart rate, heart rate variability, and PR, QRS, and QT intervals. Fetal ECG reflects the intimate relationship between the cardiac nerve conduction system and the structural morphology of the heart. It seems particularly helpful in detecting the electrophysiological effects of cardiac anatomic defects (e.g. hypotrophy, hypertrophy, and conduction interruption). Fetal ECG might be a promising clinical tool to complement ultrasonography in the screening program for CHD. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Incidence of fetal bradycardia and effect of placental injury on fetal heart rate during second-trimester genetic amniocentesis.

    PubMed

    Hanprasertpong, T; Petpichetchian, C; Ponglopisit, S; Suksai, M; Kor-Anantakul, O; Geater, A; Pruksanusak, N; Hanprasertpong, J

    2016-05-01

    A prospective study was conducted for comparing the incidence of fetal bradycardia and level of fetal heart rate change following a second-trimester genetic amniocentesis with and without placental injury. A total of 257 and 495 participants in injured and non-injured groups were analysed. The incidence of fetal bradycardia following amniocentesis was not statistically different between the two groups (1.17%, [95% CI 0.24, 3.37] and 0.20%, [95% CI 0.005, 1.12]) in injured and non-injured placenta groups, respectively; p = 0.118). The mean change in baseline fetal heart rate before and after amniocentesis was also not significantly different between the two groups (p = 0.844). No fetal death or pregnancy loss occurred within 4 weeks after the procedure. All 4 bradycardia participants were normal and healthy and had an appropriate weight for their gestational age. We conclude that placental injury during a second-trimester genetic amniocentesis due to advanced maternal age poses only a low risk of fetal bradycardia, and there is no evidence of differences between subjects with injured and non-injured placenta in the changes in fetal heart rate.

  5. [Effect of hyperglycaemia on fetal heart in pregnant rats].

    PubMed

    Zou, Yan; Ding, Yiling

    2009-02-01

    To investigate the effect of hyperglycaemia on the cardiomyodial change of rat fetus. Thirty clean SD pregnant rats were randomly dividing into group A, B and C, 10 in each group. Group A were injected intraperitoneally 50 mg/kg streptozotocin on the 6th day of pregnancy, Group B were injected the same dose on the 13th day of pregnancy, while Group C were injected intraperitoneally 0.1 mmol/L citrate buffer solution on the 6th day of pregnancy. All rats were killed on the 21st day of pregnancy, the total fetus, live fetus, weight, and length of fetus were recorded. The blood glucose in the fetal rats was measured, and the fetal hearts were collected. The fetal hearts were pathologically examined under light microscope and electron microscope. Immunohistochemical staining was applied to determine Caspase-3 in the heart of fetus. (1) The blood glucose of pregnant rats in the 3 groups showed no difference before intervening (P>0.05). There was significant difference between Group A and C, Group B and C after intervening (P<0.01), but no significant difference between Group A and B was found (P>0.05). (2 )The fetus in Group A and B was heavier and longer than in Group C, with significant difference (P<0.01), but not between Group A and B (P>0.05). The blood glucose of fetus in Group A and B was lower than that in Group C, with significant difference (P<0.01), but not between Group A and B (P>0.05). The rate of fetal death in Group A, B, and C were 31.96%,12.84%, and 3.88%, respectively. Significant deviation existed in the 3 groups (P<0.01). (3) Under light microscope, fetal hearts in Group A and B showed disorder, cardiac muscle cells swelled. There were vacuoles in cytolymph and necrosis in the myocardial tissue. Significant deviation in the integral of fetal necrosis existed in the 3 groups (P<0.01). (4) Caspase-3 was detected in the fetal hearts, the positive area ratio and mean OD value had significant deviation in the 3 groups (P<0.01).(5) Under the electron

  6. [Detection of Heart Rate of Fetal ECG Based on STFT and BSS].

    PubMed

    Wang, Xu; Cai, Kun

    2016-01-01

    Changes in heart rate of fetal is function regulating performance of the circulatory system and the central nervous system, it is significant to detect heart rate of fetus in perinatal fetal. This paper puts forward the fetal heart rate detection method based on short time Fourier transform and blind source separation. First of all, the mixed ECG signal was preprocessed, and then the wavelet transform technique was used to separate the fetal ECG signal with noise from mixed ECG signal, after that, the short-time Fourier transform and the blind separation were carried on it, and then calculated the correlation coefficient of it, Finally, An independent component that it has strongest correlation with the original signal was selected to make FECG peak detection and calculated the fetal instantaneous heart rate. The experimental results show that the method can improve the detection rate of the FECG peak (R), and it has high accuracy in fixing peak(R) location in the case of low signal-noise ratio.

  7. Online detection of fetal acidemia during labour by testing synchronization of EEG and heart rate: a prospective study in fetal sheep.

    PubMed

    Wang, Xiaogang; Durosier, L Daniel; Ross, Michael G; Richardson, Bryan S; Frasch, Martin G

    2014-01-01

    Severe fetal acidemia during labour can result in life-lasting neurological deficits, but the timely detection of this condition is often not possible. This is because the positive predictive value (PPV) of fetal heart rate (FHR) monitoring, the mainstay of fetal health surveillance during labour, to detect concerning fetal acidemia is around 50%. In fetal sheep model of human labour, we reported that severe fetal acidemia (pH<7.00) during repetitive umbilical cord occlusions (UCOs) is preceded ∼60 minutes by the synchronization of electroencephalogram (EEG) and FHR. However, EEG and FHR are cyclic and noisy, and although the synchronization might be visually evident, it is challenging to detect automatically, a necessary condition for bedside utility. Here we present and validate a novel non-parametric statistical method to detect fetal acidemia during labour by using EEG and FHR. The underlying algorithm handles non-stationary and noisy data by recording number of abnormal episodes in both EEG and FHR. A logistic regression is then deployed to test whether these episodes are significantly related to each other. We then apply the method in a prospective study of human labour using fetal sheep model (n = 20). Our results render a PPV of 68% for detecting impending severe fetal acidemia ∼60 min prior to pH drop to less than 7.00 with 100% negative predictive value. We conclude that this method has a great potential to improve PPV for detection of fetal acidemia when it is implemented at the bedside. We outline directions for further refinement of the algorithm that will be achieved by analyzing larger data sets acquired in prospective human pilot studies.

  8. Maternal physical activity mode and fetal heart outcome.

    PubMed

    May, Linda E; Suminski, Richard R; Berry, Andrew; Langaker, Michelle D; Gustafson, Kathleen M

    2014-07-01

    Maternal leisure-time physical activity (LTPA) improves cardiac autonomic function in the fetus. The specific physical activity attributes (e.g., mode) that produce this benefit are not well understood. To determine if more time spent performing non-continuous LTPA during pregnancy is significantly associated with lower fetal heart rate (HR) and increased heart rate variability (HRV). This paper presents a retrospective analysis of previously reported data. Fetal magnetocardiograms (MCG) were recorded from 40 pregnant women at 36-wk gestational age. Metrics of fetal HR and HRV, self-reported min of continuous and non-continuous LTPA performed during the 3-months preceding the 36-wk assessment point and covariates (maternal weight change pre to 36-wk, age, and resting HR and fetal activity state during MCG recordings. Positive correlations were significant (p<0.05) between min of continuous LTPA, the time domain metrics that describe fetal overall HRV, short-term HRV and a frequency domain metric that reflects vagal activity. Time spent in non-continuous LTPA was positively correlated (p<0.05) with two HRV metrics that reflect fetal overall HRV. In the multiple regression analyses, minutes of non-continuous LTPA remained associated with fetal vagal activity (p<0.05) and the relationships between minutes of non-continuous LTPA and fetal overall HRV (p<0.005) persisted. These data suggest non-continuous physical activity provides unique benefits to the fetal autonomic nervous system that may give the fetus an adaptive advantage. Further studies are needed to understand the physiological mechanisms and long-term health effects of physical activity (both non-continuous and continuous) performed during pregnancy to both women and their offspring. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Linear Phase Sharp Transition BPF to Detect Noninvasive Maternal and Fetal Heart Rate.

    PubMed

    Marchon, Niyan; Naik, Gourish; Pai, K R

    2018-01-01

    Fetal heart rate (FHR) detection can be monitored using either direct fetal scalp electrode recording (invasive) or by indirect noninvasive technique. Weeks before delivery, the invasive method poses a risk factor to the fetus, while the latter provides accurate fetal ECG (FECG) information which can help diagnose fetal's well-being. Our technique employs variable order linear phase sharp transition (LPST) FIR band-pass filter which shows improved stopband attenuation at higher filter orders. The fetal frequency fiduciary edges form the band edges of the filter characterized by varying amounts of overlap of maternal ECG (MECG) spectrum. The one with the minimum maternal spectrum overlap was found to be optimum with no power line interference and maximum fetal heart beats being detected. The improved filtering is reflected in the enhancement of the performance of the fetal QRS detector (FQRS). The improvement has also occurred in fetal heart rate obtained using our algorithm which is in close agreement with the true reference (i.e., invasive fetal scalp ECG). The performance parameters of the FQRS detector such as sensitivity (Se), positive predictive value (PPV), and accuracy (F 1 ) were found to improve even for lower filter order. The same technique was extended to evaluate maternal QRS detector (MQRS) and found to yield satisfactory maternal heart rate (MHR) results.

  10. Fetal heart rate changes associated with general anesthesia.

    PubMed

    Fedorkow, D M; Stewart, T J; Parboosingh, J

    1989-07-01

    Decreased fetal heart rate variability was noted 90 seconds after the induction of general anesthesia with sodium thiopentone and fentanyl in a patient undergoing basket extraction of a renal calculus at 30 weeks' gestation. The fetal sleep pattern lasted for 105 minutes after the anesthetic was discontinued, 45 minutes after the mother was fully awake.

  11. PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

    PubMed

    Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

    2014-10-01

    In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. © 2014 Society for Endocrinology.

  12. Peroxisome Proliferator-Activated Receptors Alpha, Beta, and Gamma mRNA and Protein Expression in Human Fetal Tissues

    PubMed Central

    Abbott, Barbara D.; Wood, Carmen R.; Watkins, Andrew M.; Das, Kaberi P.; Lau, Christopher S.

    2010-01-01

    Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose homeostasis, are targets of pharmaceuticals, and are also activated by environmental contaminants. Almost nothing is known about expression of PPARs during human fetal development. This study examines expression of PPARα, β, and γ mRNA and protein in human fetal tissues. With increasing fetal age, mRNA expression of PPARα and β increased in liver, but PPARβ decreased in heart and intestine, and PPARγ decreased in adrenal. Adult and fetal mean expression of PPARα, β, and γ mRNA did not differ in intestine, but expression was lower in fetal stomach and heart. PPARα and β mRNA in kidney and spleen, and PPARγ mRNA in lung and adrenal were lower in fetal versus adult. PPARγ in liver and PPARβ mRNA in thymus were higher in fetal versus adult. PPARα protein increased with fetal age in intestine and decreased in lung, kidney, and adrenal. PPARβ protein in adrenal and PPARγ in kidney decreased with fetal age. This study provides new information on expression of PPAR subtypes during human development and will be important in evaluating the potential for the developing human to respond to PPAR environmental or pharmaceutical agonists. PMID:20706641

  13. Assessing effects of BL67 points stimulation on fetal heart rate parameters and fetal movements during nonstress test.

    PubMed

    Pirhadi, Masume; Valiani, Mahboube

    2017-01-01

    One of the main goals of antenatal testing is to identify fetuses at the risk of neurologic injury or death so that these adverse outcomes can be prevented. We want to assess the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements during nonstress test (NST). We did a quasi-experimental design in Shahid Beheshti Hospital in Isfahan in 2011. This study aims to assessment of the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements. We did a randomized controlled clinical trial in Shahid Beheshti Hospital in Isfahan in 2011. This study is a quasi-experimental design that was conducted in one group and the two steps (before-after study). Participants were pregnant women (primigravida) who were 35-18 years that refer to Shahid Beheshti Hospital in Isfahan in 2011 to receive routine prenatal care. The 32 pregnant women were selected for acupressure during the second NST. The statistical processing was performed by descriptive, paired t -test through SPSS version 20. There was no significant difference in mean number of accelerations in fetal heart rate and mean number of fetal movement before and after intervention; however, there was a significant difference in mean time to the second acceleration before and after the intervention ( P = 0.04). No difference between parameters of the fetal heart rate before and after stimulation and lack of uterine response by this method is a significant advantage and is probably why stimulating this point could not create a risk to the fetuses.

  14. Fetal Intelligent Navigation Echocardiography (FINE): a novel method for rapid, simple, and automatic examination of the fetal heart.

    PubMed

    Yeo, Lami; Romero, Roberto

    2013-09-01

    To describe a novel method (Fetal Intelligent Navigation Echocardiography (FINE)) for visualization of standard fetal echocardiography views from volume datasets obtained with spatiotemporal image correlation (STIC) and application of 'intelligent navigation' technology. We developed a method to: 1) demonstrate nine cardiac diagnostic planes; and 2) spontaneously navigate the anatomy surrounding each of the nine cardiac diagnostic planes (Virtual Intelligent Sonographer Assistance (VIS-Assistance®)). The method consists of marking seven anatomical structures of the fetal heart. The following echocardiography views are then automatically generated: 1) four chamber; 2) five chamber; 3) left ventricular outflow tract; 4) short-axis view of great vessels/right ventricular outflow tract; 5) three vessels and trachea; 6) abdomen/stomach; 7) ductal arch; 8) aortic arch; and 9) superior and inferior vena cava. The FINE method was tested in a separate set of 50 STIC volumes of normal hearts (18.6-37.2 weeks of gestation), and visualization rates for fetal echocardiography views using diagnostic planes and/or VIS-Assistance® were calculated. To examine the feasibility of identifying abnormal cardiac anatomy, we tested the method in four cases with proven congenital heart defects (coarctation of aorta, tetralogy of Fallot, transposition of great vessels and pulmonary atresia with intact ventricular septum). In normal cases, the FINE method was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 78-100% of cases; 2) VIS-Assistance® in 98-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance® in 98-100% of cases. In all four abnormal cases, the FINE method demonstrated evidence of abnormal fetal cardiac anatomy. The FINE method can be used to visualize nine standard fetal echocardiography views in normal hearts by applying 'intelligent navigation' technology to STIC volume datasets. This method can simplify

  15. A novel modality for intrapartum fetal heart rate monitoring.

    PubMed

    Ashwal, Eran; Shinar, Shiri; Aviram, Amir; Orbach, Sharon; Yogev, Yariv; Hiersch, Liran

    2017-11-02

    Intrapartum fetal heart rate (FHR) monitoring is well recommended during labor to assess fetal wellbeing. Though commonly used, the external Doppler and fetal scalp electrode monitor have significant shortcomings. Lately, non-invasive technologies were developed as possible alternatives. The objective of this study is to compare the accuracy of FHR trace using novel Electronic Uterine Monitoring (EUM) to that of external Doppler and fetal scalp electrode monitor. A comparative study conducted in a single tertiary medical center. Intrapartum FHR trace was recorded simultaneously using three different methods: internal fetal scalp electrode, external Doppler, and EUM. The latter, a multichannel electromyogram (EMG) device acquires a uterine signal and maternal and fetal electrocardiograms. FHR traces obtained from all devices during the first and second stages of labor were analyzed. Positive percent of agreement (PPA) and accuracy (by measuring root means square error between observed and predicted values) of EUM and external Doppler were both compared to internal scalp electrode monitoring. A Bland-Altman agreement plot was used to compare the differences in FHR trace between all modalities. For momentary recordings of fetal heart rate <110 bpm or >160 bpm level of agreement, sensitivity, and specificity were also evaluated. Overall, 712,800 FHR momentary recordings were obtained from 33 parturients. Although both EUM and external Doppler highly correlated with internal scalp electrode monitoring (r 2  = 0.98, p < .001 for both methods), the accuracy of EUM was significantly higher than external Doppler (99.0% versus 96.6%, p < .001). In addition, for fetal heart rate <110 bpm or >160 bpm, the PPA, sensitivity, and specificity of EUM as compared with internal fetal scalp electrode, were significantly greater than those of external Doppler (p < .001). Intrapartum FHR using EUM is both valid and accurate, yielding higher correlations with internal

  16. [Disputes and history of fetal heart monitoring].

    PubMed

    Dueñas-García, Omar Felipe; Díaz-Sotomayor, Maricela

    2011-01-01

    The concept of fetal heart monitoring to determine the fetal wellbeing state has been employed for almost 300 years, but in the last 50 years it has observed drastic changes due to the incorporation of the electronic devices that has started controversy since the moment of its description and point of start. The purpose of this article is to mention the key points and controversial moments in the history of the cardiotocography

  17. Does fractality in heart rate variability indicate the development of fetal neural processes?

    NASA Astrophysics Data System (ADS)

    Echeverría, J. C.; Woolfson, M. S.; Crowe, J. A.; Hayes-Gill, B. R.; Piéri, Jean F.; Spencer, C. J.; James, D. K.

    2004-10-01

    By using an improved detrended fluctuation analysis we studied the scaling behaviour of 53 long-term series of fetal heart rate fluctuations. Our results suggest that fractality begins to arise around 24 weeks of normal human gestation and that this condition, showing some additional developments, seems to be preserved during gestation. This may provide new evidence of a role played by cortical-to-subcortical pathways in the long-term fractal nature of heart rate variability data.

  18. The role of abnormal fetal heart rate in scheduling chorionic villus sampling.

    PubMed

    Yagel, S; Anteby, E; Ron, M; Hochner-Celnikier, D; Achiron, R

    1992-09-01

    To assess the value of fetal heart rate (FHR) measurements in predicting spontaneous fetal loss in pregnancies scheduled for chorionic villus sampling (CVS). A prospective descriptive study. Two hospital departments of obstetrics and gynaecology in Israel. 114 women between 9 and 11 weeks gestation scheduled for chorionic villus sampling (CVS). Fetal heart rate was measured by transvaginal Doppler ultrasound and compared with a monogram established from 75 fetuses. Whenever a normal FHR was recorded, CVS was performed immediately. 106 women had a normal FHR and underwent CVS; two of these pregnancies ended in miscarriage. In five pregnancies no fetal heart beats could be identified and fetal death was diagnosed. In three pregnancies an abnormal FHR was recorded and CVS was postponed; all three pregnancies ended in miscarriage within 2 weeks. Determination of FHR correlated with crown-rump length could be useful in predicting spontaneous miscarriage before performing any invasive procedure late in the first trimester.

  19. The limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia.

    PubMed

    Clark, Steven L; Hamilton, Emily F; Garite, Thomas J; Timmins, Audra; Warrick, Philip A; Smith, Samuel

    2017-02-01

    Despite intensive efforts directed at initial training in fetal heart rate interpretation, continuing medical education, board certification/recertification, team training, and the development of specific protocols for the management of abnormal fetal heart rate patterns, the goals of consistently preventing hypoxia-induced fetal metabolic acidemia and neurologic injury remain elusive. The purpose of this study was to validate a recently published algorithm for the management of category II fetal heart rate tracings, to examine reasons for the birth of infants with significant metabolic acidemia despite the use of electronic fetal heart rate monitoring, and to examine critically the limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia. The potential performance of electronic fetal heart rate monitoring under ideal circumstances was evaluated in an outcomes-blinded examination fetal heart rate tracing of infants with metabolic acidemia at birth (base deficit, >12) and matched control infants (base deficit, <8) under the following conditions: (1) expert primary interpretation, (2) use of a published algorithm that was developed and endorsed by a large group of national experts, (3) assumption of a 30-minute period of evaluation for noncritical category II fetal heart rate tracings, followed by delivery within 30 minutes, (4) evaluation without the need to provide patient care simultaneously, and (5) comparison of results under these circumstances with those achieved in actual clinical practice. During the study period, 120 infants were identified with an arterial cord blood base deficit of >12 mM/L. Matched control infants were not demographically different from subjects. In actual practice, operative intervention on the basis of an abnormal fetal heart rate tracings occurred in 36 of 120 fetuses (30.0%) with metabolic acidemia. Based on expert, algorithm-assisted reviews, 55 of 120 patients with acidemia (45.8%) were

  20. Effect of maternal position on fetal behavioural state and heart rate variability in healthy late gestation pregnancy

    PubMed Central

    Burgess, Wendy; McIntyre, Jordan P. R.; Gunn, Alistair J.; Lear, Christopher A.; Bennet, Laura; Mitchell, Edwin A.; Thompson, John M. D.

    2016-01-01

    Key points Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position.Fetal state 1F is more likely to occur in maternal supine or right lateral positions.Fetal state 4F is less likely to occur when the woman lies supine or semi‐recumbent.Fetal state change is more likely when the woman is supine or semi‐recumbent.Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi‐recumbent positions. Abstract Fetal behavioural states (FBS) are measures of fetal wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen consuming state with changes in the cardiotocograph and reduced fetal activity. Recent studies of late gestation stillbirth described the importance of sleep position in the risk of intrauterine death. We designed this study to assess the effects of different maternal positions on FBS in healthy late gestation pregnancies under controlled conditions. Twenty‐nine healthy women had continuous fetal ECG recordings under standardized conditions in four randomly allocated positions, left lateral, right lateral, supine and semi‐recumbent. Two blinded observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate variability were calculated from ECG beat to beat data. Compared to state 2F, state 4F was less likely to occur when women were semi‐recumbent [odds ratio (OR) = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95% CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11, 5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State change was more likely when the mother was semi‐recumbent (OR = 2.17, 95% CI 1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant association of maternal position to mean fetal heart rate. The measures of heart rate variability (SDNN and RMSSD) were reduced in both semi‐recumbent and supine positions. In

  1. Effect of maternal position on fetal behavioural state and heart rate variability in healthy late gestation pregnancy.

    PubMed

    Stone, Peter R; Burgess, Wendy; McIntyre, Jordan P R; Gunn, Alistair J; Lear, Christopher A; Bennet, Laura; Mitchell, Edwin A; Thompson, John M D

    2017-02-15

    Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position. Fetal state 1F is more likely to occur in maternal supine or right lateral positions. Fetal state 4F is less likely to occur when the woman lies supine or semi-recumbent. Fetal state change is more likely when the woman is supine or semi-recumbent. Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi-recumbent positions. Fetal behavioural states (FBS) are measures of fetal wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen consuming state with changes in the cardiotocograph and reduced fetal activity. Recent studies of late gestation stillbirth described the importance of sleep position in the risk of intrauterine death. We designed this study to assess the effects of different maternal positions on FBS in healthy late gestation pregnancies under controlled conditions. Twenty-nine healthy women had continuous fetal ECG recordings under standardized conditions in four randomly allocated positions, left lateral, right lateral, supine and semi-recumbent. Two blinded observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate variability were calculated from ECG beat to beat data. Compared to state 2F, state 4F was less likely to occur when women were semi-recumbent [odds ratio (OR) = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95% CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11, 5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State change was more likely when the mother was semi-recumbent (OR = 2.17, 95% CI 1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant association of maternal position to mean fetal heart rate. The measures of heart rate variability (SDNN and RMSSD) were reduced in both semi-recumbent and supine positions. In healthy late gestation pregnancy

  2. [Effect of Music Intervention on Maternal Anxiety and Fetal Heart Rate Pattern During Non-Stress Test].

    PubMed

    Oh, Myung Ok; Kim, Young Jeoum; Baek, Cho Hee; Kim, Ju Hee; Park, No Mi; Yu, Mi Jeong; Song, Han Sol

    2016-06-01

    The purpose of this cross-over experimental study was to examine effects of music intervention on maternal anxiety, fetal heart rate pattern and testing time during non-stress tests (NST) for antenatal fetal assessment. Sixty pregnant women within 28 to 40 gestational weeks were randomly assigned to either the experimental group (n=30) or control group (n=30). Music intervention was provided to pregnant women in the experimental group during NST. Degree of maternal anxiety and fetal heart rate pattern were our primary outcomes. State-trait anxiety inventory, blood pressure, pulse rate, and changes in peripheral skin temperature were assessed to determine the degree of maternal anxiety. Baseline fetal heart rate, frequency of acceleration in fetal heart rate, fetal movement test and testing time for reactive NST were assessed to measure the fetal heart rate pattern. The experimental group showed significantly lower scores in state anxiety than the control group. There were no significant differences in systolic blood pressure and pulse rate between the two groups. Baseline fetal heart rate was significantly lower in the experimental group than in the control group. Frequency of acceleration in fetal heart rate was significantly increased in the experimental group compared to the control group. There were no significant differences in fetal movement and testing time for reactive NST between the two groups. Present results suggest that music intervention could be an effective nursing intervention for alel viating anxiety during non-stress test.

  3. A Comparative Study on Fetal Heart Rates Estimated from Fetal Phonography and Cardiotocography

    PubMed Central

    Ibrahim, Emad A.; Al Awar, Shamsa; Balayah, Zuhur H.; Hadjileontiadis, Leontios J.; Khandoker, Ahsan H.

    2017-01-01

    The aim of this study is to investigate that fetal heart rates (fHR) extracted from fetal phonocardiography (fPCG) could convey similar information of fHR from cardiotocography (CTG). Four-channel fPCG sensors made of low cost (<$1) ceramic piezo vibration sensor within 3D-printed casings were used to collect abdominal phonogram signals from 20 pregnant mothers (>34 weeks of gestation). A novel multi-lag covariance matrix-based eigenvalue decomposition technique was used to separate maternal breathing, fetal heart sounds (fHS) and maternal heart sounds (mHS) from abdominal phonogram signals. Prior to the fHR estimation, the fPCG signals were denoised using a multi-resolution wavelet-based filter. The proposed source separation technique was first tested in separating sources from synthetically mixed signals and then on raw abdominal phonogram signals. fHR signals extracted from fPCG signals were validated using simultaneous recorded CTG-based fHR recordings.The experimental results have shown that the fHR derived from the acquired fPCG can be used to detect periods of acceleration and deceleration, which are critical indication of the fetus' well-being. Moreover, a comparative analysis demonstrated that fHRs from CTG and fPCG signals were in good agreement (Bland Altman plot has mean = −0.21 BPM and ±2 SD = ±3) with statistical significance (p < 0.001 and Spearman correlation coefficient ρ = 0.95). The study findings show that fHR estimated from fPCG could be a reliable substitute for fHR from the CTG, opening up the possibility of a low cost monitoring tool for fetal well-being. PMID:29089896

  4. Quantifying the Interactions between Maternal and Fetal Heart Rates by Transfer Entropy.

    PubMed

    Marzbanrad, Faezeh; Kimura, Yoshitaka; Palaniswami, Marimuthu; Khandoker, Ahsan H

    2015-01-01

    Evidence of the short term relationship between maternal and fetal heart rates has been found in previous studies. However there is still limited knowledge about underlying mechanisms and patterns of the coupling throughout gestation. In this study, Transfer Entropy (TE) was used to quantify directed interactions between maternal and fetal heart rates at various time delays and gestational ages. Experimental results using maternal and fetal electrocardiograms showed significant coupling for 63 out of 65 fetuses, by statistically validating against surrogate pairs. Analysis of TE showed a decrease in transfer of information from fetus to the mother with gestational age, alongside the maturation of the fetus. On the other hand, maternal to fetal TE was significantly greater in mid (26-31 weeks) and late (32-41 weeks) gestation compared to early (16-25 weeks) gestation (Mann Whitney Wilcoxon (MWW) p<0.05). TE further increased from mid to late, for the fetuses with RMSSD of fetal heart rate being larger than 4 msec in the late gestation. This difference was not observed for the fetuses with smaller RMSSD, which could be associated with the quiet sleep state. Delay in the information transfer from mother to fetus significantly decreased (p = 0.03) from mid to late gestation, implying a decrease in fetal response time. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. The effect of maternal respiratory rate derived from maternal ECG was also investigated and no significant relationship was found between breathing rate and TE at any lag. In conclusion, the application of TE with delays revealed detailed information on the fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.

  5. Quantifying the Interactions between Maternal and Fetal Heart Rates by Transfer Entropy

    PubMed Central

    Marzbanrad, Faezeh; Kimura, Yoshitaka; Palaniswami, Marimuthu; Khandoker, Ahsan H.

    2015-01-01

    Evidence of the short term relationship between maternal and fetal heart rates has been found in previous studies. However there is still limited knowledge about underlying mechanisms and patterns of the coupling throughout gestation. In this study, Transfer Entropy (TE) was used to quantify directed interactions between maternal and fetal heart rates at various time delays and gestational ages. Experimental results using maternal and fetal electrocardiograms showed significant coupling for 63 out of 65 fetuses, by statistically validating against surrogate pairs. Analysis of TE showed a decrease in transfer of information from fetus to the mother with gestational age, alongside the maturation of the fetus. On the other hand, maternal to fetal TE was significantly greater in mid (26–31 weeks) and late (32–41 weeks) gestation compared to early (16–25 weeks) gestation (Mann Whitney Wilcoxon (MWW) p<0.05). TE further increased from mid to late, for the fetuses with RMSSD of fetal heart rate being larger than 4 msec in the late gestation. This difference was not observed for the fetuses with smaller RMSSD, which could be associated with the quiet sleep state. Delay in the information transfer from mother to fetus significantly decreased (p = 0.03) from mid to late gestation, implying a decrease in fetal response time. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. The effect of maternal respiratory rate derived from maternal ECG was also investigated and no significant relationship was found between breathing rate and TE at any lag. In conclusion, the application of TE with delays revealed detailed information on the fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being. PMID:26701122

  6. Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

    PubMed Central

    Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

    2016-01-01

    Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms

  7. Exploring the Relationship between Fetal Heart Rate and Cognition

    ERIC Educational Resources Information Center

    Kisilevsky, Barbara S.; Hains, Sylvia M. J.

    2010-01-01

    A relationship between fetal heart rate (HR) and cognition is explored within the context of infant, child and adult studies where the association is well established. Lack of direct access to the fetus and maturational changes limit research paradigms and response measures for fetal studies. Nevertheless, neural regulation of HR shows a number of…

  8. Simultaneous monitoring of maternal and fetal heart rate variability during labor in relation with fetal gender.

    PubMed

    Gonçalves, Hernâni; Fernandes, Diana; Pinto, Paula; Ayres-de-Campos, Diogo; Bernardes, João

    2017-11-01

    Male gender is considered a risk factor for several adverse perinatal outcomes. Fetal gender effect on fetal heart rate (FHR) has been subject of several studies with contradictory results. The importance of maternal heart rate (MHR) monitoring during labor has also been investigated, but less is known about the effect of fetal gender on MHR. The aim of this study is to simultaneously assess maternal and FHR variability during labor in relation with fetal gender. Simultaneous MHR and FHR recordings were obtained from 44 singleton term pregnancies during the last 2 hr of labor (H 1, H 2 ). Heart rate tracings were analyzed using linear (time- and frequency-domain) and nonlinear indices. Both linear and nonlinear components were considered in assessing FHR and MHR interaction, including cross-sample entropy (cross-SampEn). Mothers carrying male fetuses (n = 22) had significantly higher values for linear indices related with MHR average and variability and sympatho-vagal balance, while the opposite occurred in the high-frequency component and most nonlinear indices. Significant differences in FHR were only observed in H 1 with higher entropy values in female fetuses. Assessing the differences between FHR and MHR, statistically significant differences were obtained in most nonlinear indices between genders. A significantly higher cross-SampEn was observed in mothers carrying female fetuses (n = 22), denoting lower synchrony or similarity between MHR and FHR. The variability of MHR and the synchrony/similarity between MHR and FHR vary with respect to fetal gender during labor. These findings suggest that fetal gender needs to be taken into account when simultaneously monitoring MHR and FHR. © 2017 Wiley Periodicals, Inc.

  9. [Estimation of the atrioventricular time interval by pulse Doppler in the normal fetal heart].

    PubMed

    Hamela-Olkowska, Anita; Dangel, Joanna

    2009-08-01

    To assess normative values of the fetal atrioventricular (AV) time interval by pulse-wave Doppler methods on 5-chamber view. Fetal echocardiography exams were performed using Acuson Sequoia 512 in 140 singleton fetuses at 18 to 40 weeks of gestation with sinus rhythm and normal cardiac and extracardiac anatomy. Pulsed Doppler derived AV intervals were measured from left ventricular inflow/outflow view using transabdominal convex 3.5-6 MHz probe. The values of AV time interval ranged from 100 to 150 ms (mean 123 +/- 11.2). The AV interval was negatively correlated with the heart rhythm (p<0.001). Fetal heart rate decreased as gestation progressed (p<0.001). Thus, the AV intervals increased with the age of gestation (p=0.007). However, in the same subgroup of the fetal heart rate there was no relation between AV intervals and gestational age. Therefore, the AV intervals showed only the heart rate dependence. The 95th percentiles of AV intervals according to FHR ranged from 135 to 148 ms. 1. The AV interval duration was negatively correlated with the heart rhythm. 2. Measurement of AV time interval is easy to perform and has a good reproducibility. It may be used for the fetal heart block screening in anti-Ro and anti-La positive pregnancies. 3. Normative values established in the study may help obstetricians in assessing fetal abnormalities of the AV conduction.

  10. Acoustically based fetal heart rate monitor

    NASA Technical Reports Server (NTRS)

    Baker, Donald A.; Zuckerwar, Allan J.

    1991-01-01

    The acoustically based fetal heart rate monitor permits an expectant mother to perform the fetal Non-Stress Test in her home. The potential market would include the one million U.S. pregnancies per year requiring this type of prenatal surveillance. The monitor uses polyvinylidene fluoride (PVF2) piezoelectric polymer film for the acoustic sensors, which are mounted in a seven-element array on a cummerbund. Evaluation of the sensor ouput signals utilizes a digital signal processor, which performs a linear prediction routine in real time. Clinical tests reveal that the acoustically based monitor provides Non-Stress Test records which are comparable to those obtained with a commercial ultrasonic transducer.

  11. Aerobic Exercise during Pregnancy and Presence of Fetal-Maternal Heart Rate Synchronization

    PubMed Central

    Van Leeuwen, Peter; Gustafson, Kathleen M.; Cysarz, Dirk; Geue, Daniel; May, Linda E.; Grönemeyer, Dietrich

    2014-01-01

    It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization. Methods In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance. Results In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data. Conclusion The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates. PMID:25162592

  12. Aerobic exercise during pregnancy and presence of fetal-maternal heart rate synchronization.

    PubMed

    Van Leeuwen, Peter; Gustafson, Kathleen M; Cysarz, Dirk; Geue, Daniel; May, Linda E; Grönemeyer, Dietrich

    2014-01-01

    It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization. In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance. In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data. The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates.

  13. Third trimester fetal heart rate predicts phenotype and mutation burden in the type 1 long QT syndrome.

    PubMed

    Winbo, Annika; Fosdal, Inger; Lindh, Maria; Diamant, Ulla-Britt; Persson, Johan; Wettrell, Göran; Rydberg, Annika

    2015-08-01

    Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype. This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110 KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29-41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=-0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (-10 beats per minute per added mutation; P<1.0×10(-23)). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted -7 beats per minute, P<0.0001. In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias. © 2015 American Heart Association, Inc.

  14. Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

    PubMed

    Soncini, Emanuele; Paganelli, Simone; Vezzani, Cristina; Gargano, Giancarlo; Giovanni Battista, La Sala

    2014-09-01

    To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥ 37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. The mean values of pH and base excess decreased proportionally as tracings worsened (p < 0.001). The duration of at least 30 min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤-12 mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50 min. Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

  15. Development of multiscale complexity and multifractality of fetal heart rate variability.

    PubMed

    Gierałtowski, Jan; Hoyer, Dirk; Tetschke, Florian; Nowack, Samuel; Schneider, Uwe; Zebrowski, Jan

    2013-11-01

    During fetal development a complex system grows and coordination over multiple time scales is formed towards an integrated behavior of the organism. Since essential cardiovascular and associated coordination is mediated by the autonomic nervous system (ANS) and the ANS activity is reflected in recordable heart rate patterns, multiscale heart rate analysis is a tool predestined for the diagnosis of prenatal maturation. The analyses over multiple time scales requires sufficiently long data sets while the recordings of fetal heart rate as well as the behavioral states studied are themselves short. Care must be taken that the analysis methods used are appropriate for short data lengths. We investigated multiscale entropy and multifractal scaling exponents from 30 minute recordings of 27 normal fetuses, aged between 23 and 38 weeks of gestational age (WGA) during the quiet state. In multiscale entropy, we found complexity lower than that of non-correlated white noise over all 20 coarse graining time scales investigated. Significant maturation age related complexity increase was strongest expressed at scale 2, both using sample entropy and generalized mutual information as complexity estimates. Multiscale multifractal analysis (MMA) in which the Hurst surface h(q,s) is calculated, where q is the multifractal parameter and s is the scale, was applied to the fetal heart rate data. MMA is a method derived from detrended fluctuation analysis (DFA). We modified the base algorithm of MMA to be applicable for short time series analysis using overlapping data windows and a reduction of the scale range. We looked for such q and s for which the Hurst exponent h(q,s) is most correlated with gestational age. We used this value of the Hurst exponent to predict the gestational age based only on fetal heart rate variability properties. Comparison with the true age of the fetus gave satisfying results (error 2.17±3.29 weeks; p<0.001; R(2)=0.52). In addition, we found that the normally

  16. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    PubMed

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  17. Canine fetal heart rate: do accelerations or decelerations predict the parturition day in bitches?

    PubMed

    Gil, E M U; Garcia, D A A; Giannico, A T; Froes, T R

    2014-10-15

    Ultrasonography is a safe and efficient technique for monitoring fetal development and viability. One of the most important and widely used parameters to verify fetal viability is the fetal heart rate (HR). In human medicine, the fetal HR normally oscillates during labor in transient accelerations and decelerations associated with uterine contractions. The present study investigated whether these variations also occur in canine fetuses and its relationship to parturition. A cohort study was conducted in 15 pregnant bitches undergoing two-dimensional high-resolution ultrasonographic examination during the 8th and 9th week of gestation. Fetal HR was assessed in M-mode for 5 minutes in each fetus in all bitches. In addition, the bitches were monitored for clinical signs of imminent parturition. Associations between the HR, antepartum time, and delivery characteristics were evaluated with a Poisson regression model. Fetal HR acceleration and deceleration occurred in canine fetuses and predicted the optimal time of parturition. These findings can help veterinarians and sonographers better understand this phenomenon in canine fetuses. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Electronic fetal heart rate monitoring and its relationship to neonatal and infant mortality in the United States.

    PubMed

    Chen, Han-Yang; Chauhan, Suneet P; Ananth, Cande V; Vintzileos, Anthony M; Abuhamad, Alfred Z

    2011-06-01

    To examine the association between electronic fetal heart rate monitoring and neonatal and infant mortality, as well as neonatal morbidity. We used the United States 2004 linked birth and infant death data. Multivariable log-binomial regression models were fitted to estimate risk ratio for association between electronic fetal heart rate monitoring and mortality, while adjusting for potential confounders. In 2004, 89% of singleton pregnancies had electronic fetal heart rate monitoring. Electronic fetal heart rate monitoring was associated with significantly lower infant mortality (adjusted relative risk, 0.75); this was mainly driven by the lower risk of early neonatal mortality (adjusted relative risk, 0.50). In low-risk pregnancies, electronic fetal heart rate monitoring was associated with decreased risk for Apgar scores <4 at 5 minutes (relative risk, 0.54); in high-risk pregnancies, with decreased risk of neonatal seizures (relative risk, 0.65). In the United States, the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity that lowered infant mortality. Copyright © 2011 Mosby, Inc. All rights reserved.

  19. Intermittent Auscultation for Intrapartum Fetal Heart Rate Surveillance: American College of Nurse-Midwives.

    PubMed

    2015-01-01

    Fetal heart rate surveillance is a standard component of intrapartum care. The fetal heart rate can be evaluated using intermittent auscultation or electronic fetal monitoring. Research that has compared these 2 strategies found them to be equivalent with respect to long-term neonatal outcomes. The purpose of this clinical bulletin by the American College of Nurse-Midwives is to review the evidence for use of intermittent auscultation and provide recommendations for intermittent auscultation technique, interpretation, and documentation. © 2015 by the American College of Nurse-Midwives.

  20. Evolving changes in fetal heart rate variability and brain injury after hypoxia-ischaemia in preterm fetal sheep.

    PubMed

    Yamaguchi, Kyohei; Lear, Christopher A; Beacom, Michael J; Ikeda, Tomoaki; Gunn, Alistair J; Bennet, Laura

    2018-01-08

    Fetal heart rate variability is a critical index of fetal wellbeing. Suppression of heart rate variability may provide prognostic information on the risk of hypoxic-ischaemic brain injury after birth. In the present study, we report the evolution of fetal heart rate variability after both mild and severe hypoxia-ischaemia. Both mild and severe hypoxia-ischaemia were associated with an initial, brief suppression of multiple measures of heart rate variability. This was followed by normal or increased levels of heart rate variability during the latent phase of injury. Severe hypoxia-ischaemia was subsequently associated with the prolonged suppression of measures of heart rate variability during the secondary phase of injury, which is the period of time when brain injury is no longer treatable. These findings suggest that a biphasic pattern of heart rate variability may be an early marker of brain injury when treatment or intervention is probably most effective. Hypoxia-ischaemia (HI) is a major contributor to preterm brain injury, although there are currently no reliable biomarkers for identifying infants who are at risk. We tested the hypothesis that fetal heart rate (FHR) and FHR variability (FHRV) would identify evolving brain injury after HI. Fetal sheep at 0.7 of gestation were subjected to either 15 (n = 10) or 25 min (n = 17) of complete umbilical cord occlusion or sham occlusion (n = 12). FHR and four measures of FHRV [short-term variation, long-term variation, standard deviation of normal to normal R-R intervals (SDNN), root mean square of successive differences) were assessed until 72 h after HI. All measures of FHRV were suppressed for the first 3-4 h in the 15 min group and 1-2 h in the 25 min group. Measures of FHRV recovered to control levels by 4 h in the 15 min group, whereas the 25 min group showed tachycardia and an increase in short-term variation and SDNN from 4 to 6 h after occlusion. The measures of FHRV then progressively

  1. Robust estimation of fetal heart rate from US Doppler signals

    NASA Astrophysics Data System (ADS)

    Voicu, Iulian; Girault, Jean-Marc; Roussel, Catherine; Decock, Aliette; Kouame, Denis

    2010-01-01

    Introduction: In utero, Monitoring of fetal wellbeing or suffering is today an open challenge, due to the high number of clinical parameters to be considered. An automatic monitoring of fetal activity, dedicated for quantifying fetal wellbeing, becomes necessary. For this purpose and in a view to supply an alternative for the Manning test, we used an ultrasound multitransducer multigate Doppler system. One important issue (and first step in our investigation) is the accurate estimation of fetal heart rate (FHR). An estimation of the FHR is obtained by evaluating the autocorrelation function of the Doppler signals for ills and healthiness foetus. However, this estimator is not enough robust since about 20% of FHR are not detected in comparison to a reference system. These non detections are principally due to the fact that the Doppler signal generated by the fetal moving is strongly disturbed by the presence of others several Doppler sources (mother' s moving, pseudo breathing, etc.). By modifying the existing method (autocorrelation method) and by proposing new time and frequency estimators used in the audio' s domain, we reduce to 5% the probability of non-detection of the fetal heart rate. These results are really encouraging and they enable us to plan the use of automatic classification techniques in order to discriminate between healthy and in suffering foetus.

  2. Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

    PubMed Central

    Wharton, J; Anderson, R H; Springall, D; Power, R F; Rose, M; Smith, A; Espejo, R; Khaghani, A; Wallwork, J; Yacoub, M H

    1988-01-01

    Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:2973340

  3. Web-based comparison of historical vs contemporary methods of fetal heart rate interpretation.

    PubMed

    Epstein, Aaron J; Iriye, Brian K; Hancock, Lyle; Quilligan, Edward J; Rumney, Pamela J; Hancock, Judy; Ghamsary, Mark; Eakin, Cortney M; Smith, Cheryl; Wing, Deborah A

    2016-10-01

    Contemporary interpretation of fetal heart rate patterns is based largely on the tenets of Drs Quilligan and Hon. This method differs from an older method that was championed by Dr Caldeyro-Barcia in recording speed and classification of decelerations. The latter uses a paper speed of 1 cm/min and classifies decelerations referent to uterine contractions as type I or II dips, compared with conventional classification as early, late, or variable with paper speed of 3 cm/min. We hypothesized that 3 cm/min speed may lead to over-analysis of fetal heart rate and that 1 cm/min may provide adequate information without compromising accuracy or efficiency. The purpose of this study was to compare the Hon-Quilligan method of fetal heart rate interpretation with the Caldeyro-Barcia method among groups of obstetrics care providers with the use of an online interactive testing tool. We deidentified 40 fetal heart rate tracings from the terminal 30 minutes before delivery. A website was created to view these tracings with the use of the standard Hon-Quilligan method and adjusted the same tracings to the 1 cm/min monitoring speed for the Caldeyro-Barcia method. We invited 2-4 caregivers to participate: maternal-fetal medicine experts, practicing maternal-fetal medicine specialists, maternal-fetal medicine fellows, obstetrics nurses, and certified nurse midwives. After completing an introductory tutorial and quiz, they were asked to interpret the fetal heart rate tracings (the order was scrambled) to manage and predict maternal and neonatal outcomes using both methods. Their results were compared with those of our expert, Edward Quilligan, and were compared among groups. Analysis was performed with the use of 3 measures: percent classification, Kappa, and adjusted Gwet-Kappa (P < .05 was considered significant). Overall, our results show from moderate to almost perfect agreement with the expert and both between and within examiners (Gwet-Kappa 0.4-0.8). The agreement at each

  4. A novel technique for fetal heart rate estimation from Doppler ultrasound signal

    PubMed Central

    2011-01-01

    Background The currently used fetal monitoring instrumentation that is based on Doppler ultrasound technique provides the fetal heart rate (FHR) signal with limited accuracy. It is particularly noticeable as significant decrease of clinically important feature - the variability of FHR signal. The aim of our work was to develop a novel efficient technique for processing of the ultrasound signal, which could estimate the cardiac cycle duration with accuracy comparable to a direct electrocardiography. Methods We have proposed a new technique which provides the true beat-to-beat values of the FHR signal through multiple measurement of a given cardiac cycle in the ultrasound signal. The method consists in three steps: the dynamic adjustment of autocorrelation window, the adaptive autocorrelation peak detection and determination of beat-to-beat intervals. The estimated fetal heart rate values and calculated indices describing variability of FHR, were compared to the reference data obtained from the direct fetal electrocardiogram, as well as to another method for FHR estimation. Results The results revealed that our method increases the accuracy in comparison to currently used fetal monitoring instrumentation, and thus enables to calculate reliable parameters describing the variability of FHR. Relating these results to the other method for FHR estimation we showed that in our approach a much lower number of measured cardiac cycles was rejected as being invalid. Conclusions The proposed method for fetal heart rate determination on a beat-to-beat basis offers a high accuracy of the heart interval measurement enabling reliable quantitative assessment of the FHR variability, at the same time reducing the number of invalid cardiac cycle measurements. PMID:21999764

  5. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association.

    PubMed

    Donofrio, Mary T; Moon-Grady, Anita J; Hornberger, Lisa K; Copel, Joshua A; Sklansky, Mark S; Abuhamad, Alfred; Cuneo, Bettina F; Huhta, James C; Jonas, Richard A; Krishnan, Anita; Lacey, Stephanie; Lee, Wesley; Michelfelder, Erik C; Rempel, Gwen R; Silverman, Norman H; Spray, Thomas L; Strasburger, Janette F; Tworetzky, Wayne; Rychik, Jack

    2014-05-27

    The goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease. A writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine. Recommendations relating to the specifics of fetal diagnosis, including the timing of referral for study, indications for referral, and experience suggested for performance and interpretation of studies, are presented. The components of a fetal echocardiogram are described in detail, including descriptions of the assessment of cardiac anatomy, cardiac function, and rhythm. Complementary modalities for fetal cardiac assessment are reviewed, including the use of advanced ultrasound techniques, fetal magnetic resonance imaging, and fetal magnetocardiography and electrocardiography for rhythm assessment. Models for parental counseling and a discussion of parental stress and depression assessments are reviewed. Available fetal therapies, including medical management for arrhythmias or heart failure and closed or open intervention for diseases affecting the cardiovascular system such as twin-twin transfusion syndrome, lung masses, and vascular tumors, are highlighted. Catheter-based intervention strategies to prevent the progression of disease in utero are also discussed. Recommendations for delivery planning strategies for fetuses with congenital heart disease including models based on classification of disease severity and delivery room

  6. Deficient maternal zinc intake-but not folate-is associated with lower fetal heart rate variability.

    PubMed

    Spann, Marisa N; Smerling, Jennifer; Gustafsson, Hanna; Foss, Sophie; Altemus, Margaret; Monk, Catherine

    2015-03-01

    Few studies of maternal prenatal diet and child development examine micronutrient status in relation to fetal assessment. Twenty-four-hour dietary recall of zinc and folate and 20min of fetal heart rate were collected from 3rd trimester pregnant adolescents. Deficient zinc was associated with less fetal heart rate variability. Deficient folate had no associations with HRV. Neither deficient zinc nor deficient folate was related to fetal heart rate. These findings, from naturalistic observation, are consistent with emerging data on prenatal zinc supplementation using a randomized control design. Taken together, the findings suggest that maternal prenatal zinc intake is an important and novel factor for understanding child ANS development. Copyright © 2015. Published by Elsevier Ireland Ltd.

  7. Information Theory to Probe Intrapartum Fetal Heart Rate Dynamics

    NASA Astrophysics Data System (ADS)

    Granero-Belinchon, Carlos; Roux, Stéphane; Abry, Patrice; Doret, Muriel; Garnier, Nicolas

    2017-11-01

    Intrapartum fetal heart rate (FHR) monitoring constitutes a reference tool in clinical practice to assess the baby health status and to detect fetal acidosis. It is usually analyzed by visual inspection grounded on FIGO criteria. Characterization of Intrapartum fetal heart rate temporal dynamics remains a challenging task and continuously receives academic research efforts. Complexity measures, often implemented with tools referred to as \\emph{Approximate Entropy} (ApEn) or \\emph{Sample Entropy} (SampEn), have regularly been reported as significant features for intrapartum FHR analysis. We explore how Information Theory, and especially {\\em auto mutual information} (AMI), is connected to ApEn and SampEn and can be used to probe FHR dynamics. Applied to a large (1404 subjects) and documented database of FHR data, collected in a French academic hospital, it is shown that i) auto mutual information outperforms ApEn and SampEn for acidosis detection in the first stage of labor and continues to yield the best performance in the second stage; ii) Shannon entropy increases as labor progresses, and is always much larger in the second stage;iii) babies suffering from fetal acidosis additionally show more structured temporal dynamics than healthy ones and that this progressive structuration can be used for early acidosis detection.

  8. Automated Fetal Heart Rate Analysis in Labor: Decelerations and Overshoots

    NASA Astrophysics Data System (ADS)

    Georgieva, A. E.; Payne, S. J.; Moulden, M.; Redman, C. W. G.

    2010-10-01

    Electronic fetal heart rate (FHR) recording is a standard way of monitoring fetal health in labor. Decelerations and accelerations usually indicate fetal distress and normality respectively. But one type of acceleration may differ, namely an overshoot that may atypically reflect fetal stress. Here we describe a new method for detecting decelerations, accelerations and overshoots as part of a novel system for computerized FHR analysis (OxSyS). There was poor agreement between clinicians when identifying these FHR features visually, which precluded setting a gold standard of interpretation. We therefore introduced `modified' Sensitivity (SE°) and `modified' Positive Predictive Value (PPV°) as appropriate performance measures with which the algorithm was optimized. The relation between overshoots and fetal compromise in labor was studied in 15 cases and 15 controls. Overshoots showed promise as an indicator of fetal compromise. Unlike ordinary accelerations, overshoots cannot be considered to be reassuring features of fetal health.

  9. Complexity analysis of fetal heart rate preceding intrauterine demise.

    PubMed

    Schnettler, William T; Goldberger, Ary L; Ralston, Steven J; Costa, Madalena

    2016-08-01

    Visual non-stress test interpretation lacks the optimal specificity and observer-agreement of an ideal screening tool for intrauterine fetal demise (IUFD) syndrome prevention. Computational methods based on traditional heart rate variability have also been of limited value. Complexity analysis probes properties of the dynamics of physiologic signals that are otherwise not accessible and, therefore, might be useful in this context. To explore the association between fetal heart rate (FHR) complexity analysis and subsequent IUFD. Our specific hypothesis is that the complexity of the fetal heart rate dynamics is lower in the IUFD group compared with controls. This case-control study utilized cases of IUFD at a single tertiary-care center among singleton pregnancies with at least 10min of continuous electronic FHR monitoring on at least 2 weekly occasions in the 3 weeks immediately prior to fetal demise. Controls delivered a live singleton beyond 35 weeks' gestation and were matched to cases by gestational age, testing indication, and maternal age in a 3:1 ratio. FHR data was analyzed using the multiscale entropy (MSE) method to derive their complexity index. In addition, pNNx, a measure of short-term heart rate variability, which in adults is ascribable primarily to cardiac vagal tone modulation, was also computed. 211 IUFDs occurred during the 9-year period of review, but only 6 met inclusion criteria. The median gestational age at the time of IUFD was 35.5 weeks. Three controls were matched to each case for a total of 24 subjects, and 87 FHR tracings were included for analysis. The median gestational age at the first fetal heart rate tracing was similar between groups (median [1st-3rd quartiles] weeks: IUFD cases: 34.7 (34.4-36.2); controls: 35.3 (34.4-36.1); p=.94). The median complexity of the cases' tracings was significantly less than the controls' (12.44 [8.9-16.77] vs. 17.82 [15.21-22.17]; p<.0001). Furthermore, the cases' median complexity decreased as

  10. Fetal QRS detection and heart rate estimation: a wavelet-based approach.

    PubMed

    Almeida, Rute; Gonçalves, Hernâni; Bernardes, João; Rocha, Ana Paula

    2014-08-01

    Fetal heart rate monitoring is used for pregnancy surveillance in obstetric units all over the world but in spite of recent advances in analysis methods, there are still inherent technical limitations that bound its contribution to the improvement of perinatal indicators. In this work, a previously published wavelet transform based QRS detector, validated over standard electrocardiogram (ECG) databases, is adapted to fetal QRS detection over abdominal fetal ECG. Maternal ECG waves were first located using the original detector and afterwards a version with parameters adapted for fetal physiology was applied to detect fetal QRS, excluding signal singularities associated with maternal heartbeats. Single lead (SL) based marks were combined in a single annotator with post processing rules (SLR) from which fetal RR and fetal heart rate (FHR) measures can be computed. Data from PhysioNet with reference fetal QRS locations was considered for validation, with SLR outperforming SL including ICA based detections. The error in estimated FHR using SLR was lower than 20 bpm for more than 80% of the processed files. The median error in 1 min based FHR estimation was 0.13 bpm, with a correlation between reference and estimated FHR of 0.48, which increased to 0.73 when considering only records for which estimated FHR > 110 bpm. This allows us to conclude that the proposed methodology is able to provide a clinically useful estimation of the FHR.

  11. Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

    PubMed

    Liu, Hai Lun; Garzoni, Luca; Herry, Christophe; Durosier, Lucien Daniel; Cao, Mingju; Burns, Patrick; Fecteau, Gilles; Desrochers, André; Patey, Natalie; Seely, Andrew J E; Faure, Christophe; Frasch, Martin G

    2016-04-01

    Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. Prospective animal study. University research laboratory. Chronically instrumented near-term fetal sheep (n = 21). Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals

  12. Fetal heart rate variation after corticosteroids for fetal maturation.

    PubMed

    Knaven, Olga; Ganzevoort, Wessel; de Boer, Marjon; Wolf, Hans

    2017-09-01

    Several studies report a decrease of fetal heart rate (FHR) short-term variation (STV) after corticosteroids for improvement of fetal maturity and advice not to deliver a fetus for low STV within 2-3days after corticosteroids. However, literature is not unanimous in this respect. This study intends to asses STV longitudinally after corticosteroid administration. A retrospective cohort study in a tertiary perinatal centre from 2009 to 2015 included all women who had been treated with corticosteroids at gestational age of 26-34 weeks, had a computerized cardiotocography (cCTG) before and after medication and did not deliver within 48h. FHR and STV were stratified over 12-h periods and compared before and after corticosteroids. Women with imminent preterm labour (including PPROM) and women with placental problems (fetal growth restriction (FGR) or preeclampsia) (PE) were analysed separately. The effect of co-medication and gestational age was assessed. The study included 406 women, 211 with imminent preterm labour, 195 with FGR-PE. After corticosteroids STV increased 1-2ms (median 1.4; IQR 0.1-3.1) during the first 36h after start of corticosteroids. Thereafter a small decrease of less than 1ms (median -0,6; IQR -1.6 to 0.3) compared to before CC was seen. The most conspicuous effect of corticosteroids is a short term increase of STV and decrease of FHR. A slight decrease after 48-71h is possible, but abnormally low values should be considered as a sign of fetal distress. The clinical guidance, given by some, not to intervene because of a low STV after corticosteroids appears invalid. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Estimation of Measurement Characteristics of Ultrasound Fetal Heart Rate Monitor

    NASA Astrophysics Data System (ADS)

    Noguchi, Yasuaki; Mamune, Hideyuki; Sugimoto, Suguru; Yoshida, Atsushi; Sasa, Hidenori; Kobayashi, Hisaaki; Kobayashi, Mitsunao

    1995-05-01

    Ultrasound fetal heart rate monitoring is very useful to determine the status of the fetus because it is noninvasive. In order to ensure the accuracy of the fetal heart rate (FHR) obtained from the ultrasound Doppler data, we measure the fetal electrocardiogram (ECG) directly and obtain the Doppler data simultaneously. The FHR differences of the Doppler data from the direct ECG data are concentrated at 0 bpm (beats per minute), and are practically symmetrical. The distribution is found to be very close to the Student's t distribution by the test of goodness of fit with the chi-square test. The spectral density of the FHR differences shows the white noise spectrum without any dominant peaks. Furthermore, the f-n (n>1) fluctuation is observed both with the ultrasound Doppler FHR and with the direct ECG FHR. Thus, it is confirmed that the FHR observation and observation of the f-n (n>1) fluctuation using the ultrasound Doppler FHR are as useful as the direct ECG.

  14. Fetal heart rate patterns at 20 to 24 weeks gestation as recorded by fetal electrocardiography

    PubMed Central

    Hofmeyr, F; Groenewald, CA; Nel, DG; Myers, MM; Fifer, WP; Signore, C; Hankins, GDV; Odendaal, HJ

    2014-01-01

    Introduction With advancing technology it has become possible to accurately record and assess fetal heart rate (FHR) patterns from gestations as early as 20 weeks. The aim of our study was to describe early patterns of FHR, as recorded by transabdominal fetal electrocardiogram according to the Dawes-Redman criteria. Accordingly, short-term variability, basal heart rate, accelerations and decelerations were quantified at 20-24 weeks gestation among women with uncomplicated pregnancies. Methods This study was conducted in a subset of participants enrolled in a large prospective pregnancy cohort study. Our final data set consisted of 281 recordings of women with good perinatal outcomes that had undergone fetal electrocardiographic assessment as part of the Safe Passage Study. Results The success rate of the recordings was 95.4%. The mean frequency of small and large accelerations was 0.5 and 0.1 per 10 minutes respectively and that of small and large decelerations 0.3 and 0.008 per 10 minutes respectively. The mean and basal heart rates were both equal to 148.0 bpm at a median gestation of 161 days. The mean short term variation was 6.2 (SD 1.4) milliseconds and mean minute range 35.1 (SD 7.1) milliseconds. Conclusion The 20 to 24 week fetus demonstrates FHR patterns with more accelerations and decelerations, as well as higher baseline variability than was anticipated. Information from this study provides an important foundation for further, more detailed, studies of early FHR patterns. PMID:23991757

  15. Gestational diabetes alters the fetal heart rate variability during an oral glucose tolerance test: a fetal magnetocardiography study.

    PubMed

    Fehlert, E; Willmann, K; Fritsche, L; Linder, K; Mat-Husin, H; Schleger, F; Weiss, M; Kiefer-Schmidt, I; Brucker, S; Häring, H-U; Preissl, H; Fritsche, A

    2017-11-01

    Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT). We measured heart rate variability (HRV) of mothers and fetuses during a three-point OGTT using fetal magnetocardiography (fMCG). Measurements were performed in the fMEG Centre in Tübingen. After exclusion of 23 participants, 13 pregnant women with GDM and 36 pregnant women with normal glucose tolerance were examined. All women underwent the same examination setting with OGTT during which fMCG was recorded three times. Parameters of heart rate variability were measured. Compared with mothers with normal glucose regulation, mothers with GDM showed increased heart rate but no significant differences of maternal HRV. In contrast, HRV in fetuses of mothers with GDM differed from those in the metabolically healthy group regarding standard deviation normal to normal beat (SDNN) (P = 0.012), low-frequency band (P = 0.008) and high-frequency band (P = 0.031). These HRV parameters exhibit a decrease only in GDM fetuses during the second hour of the OGTT. These results show an altered response of the fetal autonomic nervous system to metabolic stress in GDM-complicated pregnancies. Hence, disturbances in maternal glucose metabolism might not only impact on the central nervous system of the fetus but may also affect the fetal autonomic nervous system. Metabolic stress reveals a different response of fetal autonomic nervous system in GDM-complicated pregnancies. © 2016 Royal College of Obstetricians and Gynaecologists.

  16. Selective heart rate variability analysis to account for uterine activity during labor and improve classification of fetal distress.

    PubMed

    Warmerdam, G J J; Vullings, R; Van Laar, J O E H; Van der Hout-Van der Jagt, M B; Bergmans, J W M; Schmitt, L; Oei, S G

    2016-08-01

    Cardiotocography (CTG) is currently the most often used technique for detection of fetal distress. Unfortunately, CTG has a poor specificity. Recent studies suggest that, in addition to CTG, information on fetal distress can be obtained from analysis of fetal heart rate variability (HRV). However, uterine contractions can strongly influence fetal HRV. The aim of this study is therefore to investigate whether HRV analysis for detection of fetal distress can be improved by distinguishing contractions from rest periods. Our results from feature selection indicate that HRV features calculated separately during contractions or during rest periods are more informative on fetal distress than HRV features that are calculated over the entire fetal heart rate. Furthermore, classification performance improved from a geometric mean of 69.0% to 79.6% when including the contraction-dependent HRV features, in addition to HRV features calculated over the entire fetal heart rate.

  17. Establishment of a database of fetal congenital heart malformations and preliminary investigation of its clinical application.

    PubMed

    Gao, Jun-Xue; Pei, Qiu-Yan; Li, Yun-Tao; Yang, Zhen-Juan

    2015-06-01

    The aim of this study was to create a database of anatomical ultrathin cross-sectional images of fetal hearts with different congenital heart diseases (CHDs) and preliminarily to investigate its clinical application. Forty Chinese fetal heart samples from induced labor due to different CHDs were cut transversely at 60-μm thickness. All thoracic organs were removed from the thoracic cavity after formalin fixation, embedded in optimum cutting temperature compound, and then frozen at -25°C for 2 hours. Subsequently, macro shots of the frozen serial sections were obtained using a digital camera in order to build a database of anatomical ultrathin cross-sectional images. Images in the database clearly displayed the fetal heart structures. After importing the images into three-dimensional software, the following functions could be realized: (1) based on the original database of transverse sections, databases of sagittal and coronal sections could be constructed; and (2) the original and constructed databases could be displayed continuously and dynamically, and rotated in arbitrary angles. They could also be displayed synchronically. The aforementioned functions of the database allowed for the retrieval of images and three-dimensional anatomy characteristics of the different fetal CHDs, and virtualization of fetal echocardiography findings. A database of 40 different cross-sectional fetal CHDs was established. An extensive database library of fetal CHDs, from which sonographers and students can study the anatomical features of fetal CHDs and virtualize fetal echocardiography findings via either centralized training or distance education, can be established in the future by accumulating further cases. Copyright © 2015. Published by Elsevier B.V.

  18. Fetal Heart Sounds Detection Using Wavelet Transform and Fractal Dimension

    PubMed Central

    Koutsiana, Elisavet; Hadjileontiadis, Leontios J.; Chouvarda, Ioanna; Khandoker, Ahsan H.

    2017-01-01

    Phonocardiography is a non-invasive technique for the detection of fetal heart sounds (fHSs). In this study, analysis of fetal phonocardiograph (fPCG) signals, in order to achieve fetal heartbeat segmentation, is proposed. The proposed approach (namely WT–FD) is a wavelet transform (WT)-based method that combines fractal dimension (FD) analysis in the WT domain for the extraction of fHSs from the underlying noise. Its adoption in this field stems from its successful use in the fields of lung and bowel sounds de-noising analysis. The efficiency of the WT–FD method in fHS extraction has been evaluated with 19 simulated fHS signals, created for the present study, with additive noise up to (3 dB), along with the simulated fPCGs database available at PhysioBank. Results have shown promising performance in the identification of the correct location and morphology of the fHSs, reaching an overall accuracy of 89% justifying the efficacy of the method. The WT–FD approach effectively extracts the fHS signals from the noisy background, paving the way for testing it in real fHSs and clearly contributing to better evaluation of the fetal heart functionality. PMID:28944222

  19. Eleven fetal echocardiographic planes using 4-dimensional ultrasound with spatio-temporal image correlation (STIC): a logical approach to fetal heart volume analysis.

    PubMed

    Jantarasaengaram, Surasak; Vairojanavong, Kittipong

    2010-09-15

    Theoretically, a cross-sectional image of any cardiac planes can be obtained from a STIC fetal heart volume dataset. We described a method to display 11 fetal echocardiographic planes from STIC volumes. Fetal heart volume datasets were acquired by transverse acquisition from 200 normal fetuses at 15 to 40 weeks of gestation. Analysis of the volume datasets using the described technique to display 11 echocardiographic planes in the multiplanar display mode were performed offline. Volume datasets from 18 fetuses were excluded due to poor image resolution. The mean visualization rates for all echocardiographic planes at 15-17, 18-22, 23-27, 28-32 and 33-40 weeks of gestation fetuses were 85.6% (range 45.2-96.8%, N = 31), 92.9% (range 64.0-100%, N = 64), 93.4% (range 51.4-100%, N = 37), 88.7%(range 54.5-100%, N = 33) and 81.8% (range 23.5-100%, N = 17) respectively. Overall, the applied technique can favorably display the pertinent echocardiographic planes. Description of the presented method provides a logical approach to explore the fetal heart volumes.

  20. Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

    PubMed Central

    DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

    2016-01-01

    Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

  1. [Usefulness of the examination of fetal blood oxygen saturation (FSpO2) and fetal heart rate (FHR) as a prognostic factor of the newborn outcome].

    PubMed

    Skoczylas, Michał; Laudański, Tadeusz

    2003-10-01

    Cardiotocography has become the standard for fetal monitoring in labor. False-positive findings during electronic fetal heart rate monitoring may were not associated with neonatal acidemia. Because of the poor specificity of fetal heart rate monitoring in predicting fetal distress, new methods are being investigated as a way to improve the accuracy of assessing the infant's condition during labor. The aim of this study was to determinate the efficiency of fetal blood oxygen saturation (FSpO2) and computer analysis of the fetal heart rate (Co-CTG) in the late 1-st stage of labor as a prognostic factor of newborn acidemia. Total 62 subjects were studied. During labors and deliveries fetal oxygen saturation was continuously recorded, with use of Nellecor N-400 fetal pulse oximeter and continous CTG were performed by Hewlett Packard 50A. Transdermal fetal oxygen saturation measurements and CTG results obtained during the labors was analyzed using MONAKO system (ITAM Zabrze). The results were compared with the values of pH and base deficit in the umbilical artery measured just after delivery. The sensitivity, specificity, negative, positive predictive values and Youden factor based on FHR and FSpO2, for prognosis of neonatal acidosis were: 65%, 80%, 16%, 97.5% 60% and 0.135 respectively FHR; and 100%, 60%, 100%, 96.8% and 0.968 respectively FSpO2. 1. The examination of fetal blood oxygen saturation in the labor is a useful prognostic factor of the newborn outcome. 2. The best predictive value for intrapartum fetal asphyxia with metabolic acidosis was found when fetal pulse oximetry is added to cardiotocography.

  2. Does maternal race influence the short-term variation of the fetal heart rate? An historical cohort study.

    PubMed

    Marie, Cécile; Sinoquet, Céline; Barasinski, Chloé; Lémery, Didier; Vendittelli, Françoise

    2015-10-01

    The main aim of this article was to analyze short-term variation (STV) of the fetal heart rate according to maternal race. The secondary aim was to study the baseline fetal heart rate according to this factor. This single-center historical cohort study covered the period from November 2008 through December 2011 (n=182). The inclusion criteria were: black women from sub-Saharan Africa or white European women, with a singleton pregnancy ≥34 weeks and fetal heart rate recorded by computerized analysis (Oxford Sonicaid System 8002) at a prenatal visit. The exclusion criteria were: medication likely to modify fetal heart rate, abnormal fetal heart rate tracing, and being in labor. A multiple linear regression analysis was used to study the association between maternal race and STV. STV was lower by 2.6ms in fetuses of black women (n=55) compared to those of white women (n=127) (8.9±2.1ms vs. 11.4±3.4ms) (p<0.001). The basal fetal heart rate was higher (p=0.001), and the recording criteria were met less often for the black women (p=0.04). After adjustment for maternal age, body mass index at the beginning of pregnancy, maternal cigarette smoking, parity, gestational diabetes, gestational age at the time of the fetal heart rate recording, and the time between the last meal and the recording, mean STV was lower by 3.1±0.6ms in fetuses of black compared with white women (p<0.001). STV is lower in fetuses of black women compared to those of white women in a low-risk population. A study of black and white women with high-risk pregnancies is necessary to assess the impact of medical practices on perinatal outcome after STV analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

    PubMed

    Segar, Jeffrey L; Volk, Ken A; Lipman, Michael H B; Scholz, Thomas D

    2013-03-01

    Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in

  4. The Effects of Meperidine Analgesia during Labor on Fetal Heart Rate

    PubMed Central

    Sekhavat, Leila; Behdad, Shecoofah

    2009-01-01

    To estimate the effects of intramuscular meperidine analgesia on fetal heart rate (FHR) patterns compared with placebo. In a prospective randomized study, 150 healthy women with singleton term pregnancy requesting analgesia during active labor were planned to receive either intramuscular meperidin 50 mg (meperidin group) or normal saline (control group) when they requested analgesia. Fetal heart rate patterns occurring within 40 minutes of initiation of labor analgesia were retrospectively read by maternal fetal medicine specialist who was blind to type of labor analgesia. Meperidine, compared with placebo, was associated with statistically significantly less beat to beat variability (absent or less than 5 beats per minute) (28% versus 5% of fetuses, P<0.05), lower proportion of accelerations (37.3% versus 17.3% P<0.05) and of the FHR. Also FHR deceleration was significantly more than control group (25.5% versus 4%, P<0.05). Meperidine has deleterious effects on FHR. PMID:23675116

  5. Human Fetal Heart Rate Dishabituation between Thirty and Thirty-Two Weeks Gestation.

    ERIC Educational Resources Information Center

    Sandman, Curt A.; Wadhwa, Pathik; Hetrick, William; Porto, Manuel; Peeke, Harmon V. S.

    1997-01-01

    Examined the ability of 32-week human fetuses to learn and recall information. Found a significant heart rate habituation pattern for a series of vibroacoustic stimuli. After a single novel stimulus, the heart rate to stimulus 1 reemerged. Uterine contractions were not related to presentation of the novel stimulus or change in heart rate after the…

  6. Early fetal heart ultrasonography as additional indicator for chromosomopathies.

    PubMed

    Dmitrovic, A; Jeremic, K; Babic, U M; Perovic, M; Mihailovic, T; Opric, D; Zecevic, N; Gojnić-Dugalić, M

    2016-01-01

    First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still

  7. Decreased baseline variability on fetal heart rate pattern in a fetus with heterotaxy syndrome.

    PubMed

    Yamada, Ryutaro; Takei, Kohta; Kaneshi, Yosuke; Morikawa, Mamoru; Cho, Kazutoshi; Minakami, Hisanori

    2015-12-01

    In a fetus with suspected heterotaxy syndrome, a decreased/absent baseline variability of fetal heart rate pattern developed at gestational week 36(+5) and continued for 5 days until birth at gestational week 37(+2), while repeat biophysical profile scorings with ultrasound were consistently unremarkable. This neonate weighing 2404 g with Apgar scores of 7 (1-min) and 8 (5-min) and umbilical arterial cord blood pH of 7.28 with base deficit of 3.9 mmol/L, showed a heart rate of 120 b.p.m. for 3 h after birth, but subsequently developed sinus bradycardia (84 b.p.m.) unresponsive to crying. Isoproterenol initiated 9 h after birth was effective in the increase of heart rate to 120 b.p.m. in this neonate. Brain magnetic resonance imaging at 16 days of age was unremarkable. The decreased/absent baseline variability of fetal heart rate pattern was speculated to have been caused by sinus node dysfunction, and not by reduced fetal oxygenation in this case. © 2015 Japan Society of Obstetrics and Gynecology.

  8. Effect of electromagnetic field emitted by cellular phones on fetal heart rate patterns.

    PubMed

    Celik, Onder; Hascalik, Seyma

    2004-01-15

    The study was planned to determine the effects of electromagnetic fields produced by cellular phones on baseline fetal heart rate, acceleration and deceleration. Forty pregnant women undergoing non-stress test were admitted to the study. Non-stress test was obtained while the subjects were holding the CP on stand by mode and on dialing mode, each for 5 min. Similar recordings were taken while there were no phones around for 10 min. Electromagnetic fields produced by cellular phones do not cause any demonstrable affect in fetal heart rate, acceleration and deceleration.

  9. Influence of carbon monoxide poisoning on the fetal heart monitor tracing: a report of 3 cases.

    PubMed

    Towers, Craig V; Corcoran, Vincent A

    2009-03-01

    The diagnosis of carbon monoxide poisoning in the third trimester of pregnancy requires an index of suspicion, and the appearance of the fetal heart monitor tracing may help in this regard. Three cases of third-trimester acute carbon monoxide poisoning occurred. In each pregnancy, the fetal heart monitor tracing on admission was correlated with the maternal carboxyhemoglobin level, and how the pattern changed following the institution of therapy was analyzed. In all 3 cases, the initial fetal heart rate pattern demonstrated decreased variability with an elevated baseline and an absence of accelerations and decelerations. Within 45-90 minutes of treatment onset, the baseline fetal heart rate dropped by 20-40 beats per minute, the variability became moderate, and accelerations occurred. Absent accelerations with minimal variability, if caused by uteroplacental insufficiency, are usually preceded by recurrent decelerations. Absent accelerations with minimal variability in the absence of recurrent decelerations may suggest another cause, of which carbon monoxide intoxication can be added to the differential, especially since this disorder often has nonspecific clinical symptoms.

  10. Linear and nonlinear measures of fetal heart rate patterns evaluated on very short fetal magnetocardiograms.

    PubMed

    Moraes, Eder Rezende; Murta, Luiz Otavio; Baffa, Oswaldo; Wakai, Ronald T; Comani, Silvia

    2012-10-01

    We analyzed the effectiveness of linear short- and long-term variability time domain parameters, an index of sympatho-vagal balance (SDNN/RMSSD) and entropy in differentiating fetal heart rate patterns (fHRPs) on the fetal heart rate (fHR) series of 5, 3 and 2 min duration reconstructed from 46 fetal magnetocardiograms. Gestational age (GA) varied from 21 to 38 weeks. FHRPs were classified based on the fHR standard deviation. In sleep states, we observed that vagal influence increased with GA, and entropy significantly increased (decreased) with GA (SDNN/RMSSD), demonstrating that a prevalence of vagal activity with autonomous nervous system maturation may be associated with increased sleep state complexity. In active wakefulness, we observed a significant negative (positive) correlation of short-term (long-term) variability parameters with SDNN/RMSSD. ANOVA statistics demonstrated that long-term irregularity and standard deviation of normal-to-normal beat intervals (SDNN) best differentiated among fHRPs. Our results confirm that short- and long-term variability parameters are useful to differentiate between quiet and active states, and that entropy improves the characterization of sleep states. All measures differentiated fHRPs more effectively on very short HR series, as a result of the fMCG high temporal resolution and of the intrinsic timescales of the events that originate the different fHRPs.

  11. STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

    PubMed

    DiPietro, Janet A; Costigan, Kathleen A; Voegtline, Kristin M

    2015-09-01

    Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

  12. Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Shows that Fetal Heart Rate Correlates with Maternal Glycemia.

    PubMed

    Cypryk, Katarzyna; Bartyzel, Lukasz; Zurawska-Klis, Monika; Mlynarski, Wojciech; Szadkowska, Agnieszka; Wilczynski, Jan; Nowakowska, Dorota; Wozniak, Lucyna A; Fendler, Wojciech

    2015-09-01

    Much evidence has shown that pregnancies in women with preexisting diabetes are affected by an increased risk of maternal and fetal adverse outcomes, probably linked to poor glycemic control. Despite great progress in medical care, the rate of stillbirths remains much higher in diabetes patients than in the general population. Recent technological advances in the field of glucose monitoring and noninvasive fetal heart rate monitoring made it possible to observe the fetal-maternal dependencies in a continuous manner. Fourteen type 1 diabetes patients were involved into the study and fitted with a blinded continuous glucose monitoring (CGM) recorder. Fetal electrocardiogram data were recorded using the Monica AN24™ device (Monica Healthcare Ltd., Nottingham, United Kingdom), the recordings of which were matched with CGM data. Statistical analysis was performed using a generalized mixed-effect logistic regression to account for individual factors. The mean number of paired data points per patient was 254±106, representing an observation period of 21.2±8.8 h. Mean glycemia equaled 5.64±0.68 mmol/L, and mean fetal heart rate was 135±6 beats/min. Higher glycemia correlated with fetal heart rate (R=0.32; P<0.0001) and was associated with higher odds of the fetus developing small accelerations (odds ratio=1.05; 95% confidence interval, 1.00-1.10; P=0.04). Elevated maternal glycemia of mothers with diabetes is associated with accelerations of fetal heart rate.

  13. Sex differences in the fetal heart rate variability indices of twins.

    PubMed

    Tendais, Iva; Figueiredo, Bárbara; Gonçalves, Hernâni; Bernardes, João; Ayres-de-Campos, Diogo; Montenegro, Nuno

    2015-03-01

    To evaluate the differences in linear and complex heart rate dynamics in twin pairs according to fetal sex combination [male-female (MF), male-male (MM), and female-female (FF)]. Fourteen twin pairs (6 MF, 3 MM, and 5 FF) were monitored between 31 and 36.4 weeks of gestation. Twenty-six fetal heart rate (FHR) recordings of both twins were simultaneously acquired and analyzed with a system for computerized analysis of cardiotocograms. Linear and nonlinear FHR indices were calculated. Overall, MM twins presented higher intrapair average in linear indices than the other pairs, whereas FF twins showed higher sympathetic-vagal balance. MF twins exhibited higher intrapair average in entropy indices and MM twins presented lower entropy values than FF twins considering the (automatically selected) threshold rLu. MM twin pairs showed higher intrapair differences in linear heart rate indices than MF and FF twins, whereas FF twins exhibited lower intrapair differences in entropy indices. The results of this exploratory study suggest that twins have sex-specific differences in linear and nonlinear indices of FHR. MM twins expressed signs of a more active autonomic nervous system and MF twins showed the most active complexity control system. These results suggest that fetal sex combination should be taken into consideration when performing detailed evaluation of the FHR in twins.

  14. ILK Induces Cardiomyogenesis in the Human Heart

    PubMed Central

    Traister, Alexandra; Aafaqi, Shabana; Masse, Stephane; Dai, Xiaojing; Li, Mark; Hinek, Aleksander; Nanthakumar, Kumaraswamy; Hannigan, Gregory; Coles, John G.

    2012-01-01

    Background Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart. Methodology/Principal Findings Primary cultures of human fetal myocardial cells (19–22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk×2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C×43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILKR211A) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILKWT). The cardiomyogenic effects of ILKR211A and ILKWT were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILKR211A and ILKWT. Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs). Conclusions/Significance In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the

  15. Application of higher-order cepstral techniques in problems of fetal heart signal extraction

    NASA Astrophysics Data System (ADS)

    Sabry-Rizk, Madiha; Zgallai, Walid; Hardiman, P.; O'Riordan, J.

    1996-10-01

    Recently, cepstral analysis based on second order statistics and homomorphic filtering techniques have been used in the adaptive decomposition of overlapping, or otherwise, and noise contaminated ECG complexes of mothers and fetals obtained by a transabdominal surface electrodes connected to a monitoring instrument, an interface card, and a PC. Differential time delays of fetal heart beats measured from a reference point located on the mother complex after transformation to cepstra domains are first obtained and this is followed by fetal heart rate variability computations. Homomorphic filtering in the complex cepstral domain and the subuent transformation to the time domain results in fetal complex recovery. However, three problems have been identified with second-order based cepstral techniques that needed rectification in this paper. These are (1) errors resulting from the phase unwrapping algorithms and leading to fetal complex perturbation, (2) the unavoidable conversion of noise statistics from Gaussianess to non-Gaussianess due to the highly non-linear nature of homomorphic transform does warrant stringent noise cancellation routines, (3) due to the aforementioned problems in (1) and (2), it is difficult to adaptively optimize windows to include all individual fetal complexes in the time domain based on amplitude thresholding routines in the complex cepstral domain (i.e. the task of `zooming' in on weak fetal complexes requires more processing time). The use of third-order based high resolution differential cepstrum technique results in recovery of the delay of the order of 120 milliseconds.

  16. Four-dimensional ultrasonography of the fetal heart with spatiotemporal image correlation.

    PubMed

    Gonçalves, Luís F; Lee, Wesley; Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Schoen, Mary Lou; Falkensammer, Peter; Treadwell, Marjorie; Romero, Roberto

    2003-12-01

    This study was undertaken to describe a new technique for the examination of the fetal heart using four-dimensional ultrasonography with spatiotemporal image correlation (STIC). Volume data sets of the fetal heart were acquired with a new cardiac gating technique (STIC), which uses automated transverse and longitudinal sweeps of the anterior chest wall. These volumes were obtained from 69 fetuses: 35 normal, 16 with congenital anomalies not affecting the cardiovascular system, and 18 with cardiac abnormalities. Dynamic multiplanar slicing and surface rendering of cardiac structures were performed. To illustrate the STIC technique, two representative volumes from a normal fetus were compared with volumes obtained from fetuses with the following congenital heart anomalies: atrioventricular septal defect, tricuspid stenosis, tricuspid atresia, and interrupted inferior vena cava with abnormal venous drainage. Volume datasets obtained with a transverse sweep were utilized to demonstrate the cardiac chambers, moderator band, interatrial and interventricular septae, atrioventricular valves, pulmonary veins, and outflow tracts. With the use of a reference dot to navigate the four-chamber view, intracardiac structures could be simultaneously studied in three orthogonal planes. The same volume dataset was used for surface rendering of the atrioventricular valves. The aortic and ductal arches were best visualized when the original plane of acquisition was sagittal. Volumes could be interactively manipulated to simultaneously visualize both outflow tracts, in addition to the aortic and ductal arches. Novel views of specific structures were generated. For example, the location and extent of a ventricular septal defect was imaged in a sagittal view of the interventricular septum. Furthermore, surface-rendered images of the atrioventricular valves were employed to distinguish between normal and pathologic conditions. Representative video clips were posted on the Journal's Web

  17. Micro-computed Tomography Provides High Accuracy Congenital Heart Disease Diagnosis in Neonatal and Fetal Mice

    PubMed Central

    Kim, Andrew J.; Francis, Richard; Liu, Xiaoqin; Devine, William A.; Ramirez, Ricardo; Anderton, Shane J.; Wong, Li Yin; Faruque, Fahim; Gabriel, George C.; Leatherbury, Linda; Tobita, Kimimasa; Lo, Cecilia W.

    2013-01-01

    Background Mice are well suited for modeling human congenital heart defects (CHD), given their four-chamber cardiac anatomy. However, mice with CHD invariably die prenatally/neonatally, causing CHD phenotypes to be missed. Therefore, we investigated the efficacy of noninvasive micro-computed tomography (micro-CT) to screen for CHD in stillborn/fetal mice. These studies were carried out using chemically mutagenized mice expected to be enriched for birth defects including CHD. Methods and Results Stillborn/fetal mice obtained from the breeding of N-ethyl-N-nitrosourea (ENU) mutagenized mice were formalin-fixed and stained with iodine, then micro-CT scanned. Those diagnosed with CHD and some CHD-negative pups were necropsied. A subset of these were further analyzed by histopathology to confirm the CHD/no-CHD diagnosis. Micro-CT scanning of 2105 fetal/newborn mice revealed an abundance of ventricular septal defects (VSD) (n=307). Overall, we observed an accuracy of 89.8% for VSD diagnosis. Outflow tract anomalies identified by micro-CT included double outlet right ventricle (n=36), transposition of the great arteries (n=14), and persistent truncus arteriosus (n=3). These were diagnosed with a 97.4% accuracy. Aortic arch anomalies also were readily detected with an overall 99.6% accuracy. This included right aortic arch (n=28) and coarctation/interrupted aortic arch (n=12). Also detected by micro-CT were atrioventricular septal defects (n=22), tricuspid hypoplasia/atresia (n=13), and coronary artery fistulas (n=16). They yielded accuracies of 98.9%, 100%, and 97.8% respectively. Conclusions Contrast enhanced micro-CT imaging in neonatal/fetal mice can reliably detect a wide spectrum of CHD. We conclude micro-CT imaging can be used for routine rapid assessments of structural heart defects in fetal/newborn mice. PMID:23759365

  18. Fetal electrocardiographic measurements in the assessment of fetal heart rate variability in the antepartum period.

    PubMed

    Van Leeuwen, Peter; Werner, Lisa; Hilal, Ziad; Schiermeier, Sven; Hatzmann, Wolfgang; Grönemeyer, Dietrich

    2014-03-01

    This study examines signal availability in fetal electrocardiogram (FECG) beat-to-beat acquisition and the accuracy of fetal heart rate variability (HRV) analysis in the clinical setting using a commercially available FECG monitor. Signal availability was examined in 130 FECG recordings of 0.3-17.5 h duration collected in 63 fetuses (25th-42nd week of gestation) under uncontrolled conditions. Identification of R-peaks demonstrated a signal loss of 30% ± 24% with 3.6 ± 1.7 signal gaps per minute. Median duration of the gaps within a recording was 1.8 ± 0.2 s. Per hour of recording, 1.8 ± 2.1 episodes of 5 min of uninterrupted data were found. Signal availability improved with gestational age and was poorer in women with high body-mass index. Fetal HRV between weeks 36-42 was examined on the basis of 5 min RR-interval episodes obtained under controlled quiet conditions in 55 FECG compared to 46 high quality fetal magnetocardiograms. There were no differences in RR-interval duration, its standard deviation and low frequency power. However, various measures of short-term HRV were significantly higher in the FECG data: root mean square of successive differences (10.0 ± 1.8 versus 6.6 ± 3.0 ms, p < 0.001, high frequency spectral power (24 ± 12 versus 13 ± 13 ms(2), p < 0.001) and approximate entropy (0.86 ± 0.16 versus 0.73 ± 0.24, p = 0.007). We conclude that, in spite of considerable signal loss, FECG recordings can accurately estimate heart rate and its overall variance. However, measures that quantify short-term beat-to-beat HRV will be compromised due to possible recurring inappropriate detection of single R-peaks.

  19. Variations from morning to afternoon of middle cerebral and umbilical artery blood flow, and fetal heart rate variability, and fetal characteristics in the normally developing fetus.

    PubMed

    Avitan, Tehila; Sanders, Ari; Brain, Ursula; Rurak, Dan; Oberlander, Tim F; Lim, Ken

    2018-05-01

    To determine if there are changes in maternal uterine blood flow, fetal brain blood flow, fetal heart rate variability, and umbilical blood flow between morning (AM) and afternoon (PM) in healthy, uncomplicated pregnancies. In this prospective study, 68 uncomplicated singleton pregnancies (mean 35 + 0.7 weeks gestation) underwent a standard observational protocol at both 08:00 (AM) and 13:30 (PM) of the same day. This protocol included Doppler measurements of uterine, umbilical, and fetal middle cerebral artery (MCA) volume flow parameters (flow, HR, peak systolic velocity [PSV], PI, and RI) followed by computerized cardiotocography. Standard descriptive statistics, χ 2 and t tests were used where appropriate. P < .05 was considered significant. A significant increase in MCA flow and MCA PSV was observed in the PM compared to the AM. This was accompanied by a fall in MCA resistance. Higher umbilical artery resistance indices were also observed in the PM compared to AM. In contrast, fetal heart rate characteristics, maternal uterine artery Doppler flow and resistance indices did not vary significantly between the AM and PM. In normal pregnancies, variations in fetal cerebral and umbilical blood flow parameters were observed between AM and PM independent of other fetal movements or baseline fetal heart rate. In contrast, uterine flow parameters remained stable across the day. These findings may have implications for the use of serial Doppler parameters used to guide clinical management in high-risk pregnancies. © 2017 Wiley Periodicals, Inc.

  20. Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

    PubMed

    Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

    2016-07-01

    Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

  1. Power spectral analysis of R-R interval variability before and during the sinusoidal heart rate pattern in fetal lambs.

    PubMed

    Suzuki, T; Okamura, K; Kimura, Y; Watanabe, T; Yaegashi, N; Murotsuki, J; Uehara, S; Yajima, A

    2000-05-01

    The appearance of the sinusoidal heart rate pattern found on fetal cardiotocograms has not been fully explained, either physiologically or clinically. In this study we performed power spectral analysis on the sinusoidal heart rate pattern obtained by administration of arginine vasopressin and atropine sulfate to investigate its frequency components in fetal lambs with long-term instrument implantation. Eleven tests were performed in 4 fetal lambs at 120 to 130 days' gestation. An artificial sinusoidal heart rate pattern was obtained by administration of atropine sulfate and arginine vasopressin in 9 tests. An autoregression model was used to compare the spectral patterns before and during the sinusoidal heart rate pattern. Marked decreases in low-frequency (0.025-0.125 cycles/beat) and high-frequency (0.2-0.5 cycles/beat) areas were observed in the presence of the sinusoidal heart rate pattern. However, there were no significant changes in the very-low-frequency area (0.01-0.025 cycles/beat), which corresponds to the frequency of the sinusoidal heart rate pattern. The sinusoidal heart rate pattern may represent a very low-frequency component inherent in fetal heart rate variability that appears when low- and high-frequency components are reduced as a result of strongly suppressed autonomic nervous activity.

  2. Dual transmission model of the fetal heart tone

    NASA Astrophysics Data System (ADS)

    Baker, Donald A.; Zuckerwar, Allan J.

    2004-05-01

    Detection of the fetal heart tone by auscultation is sometimes easy, other times very difficult. In the model proposed here, the level of difficulty depends upon the position of the fetus within the maternal abdomen. If the fetus lies in the classical left/right occiput anterior position (head down, back against the maternal abdominal wall), detection by a sensor or stethoscope on the maternal abdominal surface is easy. In this mode, named here the ``direct contact'' mode, the heartbeat pushes the fetus against the detecting sensor. The motion generates pressure by impact and does not involve acoustic propagation at all. If the fetus lies in a persistent occiput posterior position (spine-to-spine, fetus facing forward), detection is difficult. In this, the ``fluid propagation'' mode, sound generated by the fetal heart and propagating across the amniotic fluid produces extremely weak signals at the maternal surface, typically 30 dB lower than those of the direct contact mode. This reduction in tone level can be compensated by judicious selection of detection frequency band and by exploiting the difference between the background noise levels of the two modes. Experimental clinical results, demonstrating the tones associated with the two respective modes, will be presented.

  3. Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

    PubMed

    Miranda, Joana O; Ramalho, Carla; Henriques-Coelho, Tiago; Areias, José Carlos

    2017-11-01

    Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

  4. The fetal heart rate collaborative practice project: situational awareness in electronic fetal monitoring-a Kaiser Permanente Perinatal Patient Safety Program Initiative.

    PubMed

    MacEachin, S Rachel; Lopez, Connie M; Powell, Kimberly J; Corbett, Nancy L

    2009-01-01

    Electronic fetal monitoring has historically been interpreted with wide variation between and within disciplines on the obstetric healthcare team. This leads to inconsistent decision making in response to tracing interpretation. To implement a multidisciplinary electronic fetal monitoring training program, utilizing the best evidence available, enabling standardization of fetal heart rate interpretation to promote patient safety. Local multidisciplinary expertise along with an outside consultant collaborated over a series of meetings to create a multimedia instructional electronic fetal monitoring training program. After production was complete, a series of conferences attended by nurses, certified nurse midwives, and physician champions, from each hospital, attended to learn how to facilitate training at their own perinatal units. All healthcare personnel across the Kaiser Permanente perinatal program were trained in NICHD nomenclature, emergency response, interpretation guidelines, and how to create local collaborative practice agreements. Metrics for program effectiveness were measured through program evaluations from attendees, the Safety Attitudes Questionnaire. Program evaluations rendered very positive scores from both physicians and clinicians. Comparing baseline to 4 years later, the perception of safety from the staff has increased over 10% in 5 out of the 6 factors analyzed. Active participation from all disciplines in this training series has highlighted the importance of teamwork and communication. The Fetal Heart Rate Collaborative Practice Project continues to evolve utilizing other educational modalities, such as online EFM education and unit-based interdisciplinary tracing reviews.

  5. Linear and nonlinear features of fetal heart rate on the assessment of fetal development in the course of pregnancy and the impact of fetal gender.

    PubMed

    Spyridou, K; Chouvarda, I; Hadjileontiadis, L; Maglaveras, N

    2018-01-30

    This work aims to investigate the impact of gestational age and fetal gender on fetal heart rate (FHR) tracings. Different linear and nonlinear parameters indicating correlation or complexity were used to study the influence of fetal age and gender on FHR tracings. The signals were recorded from 99 normal pregnant women in a singleton pregnancy at gestational ages from 28 to 40 weeks, before the onset of labor. There were 56 female fetuses and 43 male. Analysis of FHR shows that the means as well as measures of irregularity of FHR, such as approximate entropy and algorithmic complexity, decrease as gestation progresses. There were also indications that mutual information and multiscale entropy were lower in male fetuses in early pregnancy. Fetal age and gender seem to influence FHR tracings. Taking this into consideration would improve the interpretation of FHR monitoring.

  6. The Influence of Bearing-Down Technique on the Fetal Heart Rate during the Second Stage of Labor.

    NASA Astrophysics Data System (ADS)

    Perlis, Deborah Woolley

    This experimental study contrasted the effects of sustained bearing-down efforts with short bearing-down efforts during the first twelve contractions of the second stage of labor. A single subject design with intrasubject replication was used to compare the incidence, duration, and amplitude of fetal heart rate decelerations, as well as the beat-to-beat variability of those decelerations. Neonatal outcome was evaluated with umbilical arterial cord blood pH values and the one- and five-minute APGAR scores. Thirty -two nulliparous women alternated the use of vigorous, sustained Valsalva-style bearing-down efforts with shorter efforts called minipushes every three contractions during the second stage of labor. Sixteen women began the second stage using the Valsalva-style bearing-down technique; sixteen began the second stage using the minipush. The fetal heart rate was recorded by an internal fetal scalp electrode. Uterine contractility was measured by an internal uterine pressure catheter. A repeated-measures MANOVA showed a significant interaction between the order of implementation of the bearing-down techniques and the amplitude of the fetal heart rate decelerations. A similar comparison of the duration of the decelerations showed no significant differences between the two bearing-down techniques. Likewise, analysis of the incidence of fetal heart rate decelerations and the magnitude of the beat-to-beat variability revealed no significant differences between the two techniques.

  7. Development of a piezopolymer pressure sensor for a portable fetal heart rate monitor

    NASA Technical Reports Server (NTRS)

    Zuckerwar, A. J.; Pretlow, R. A.; Stoughton, J. W.; Baker, D. A.

    1993-01-01

    A piezopolymer pressure sensor has been developed for service in a portable fetal heart rate monitor, which will permit an expectant mother to perform the fetal nonstress test, a standard predelivery test, in her home. Several sensors are mounted in an array on a belt worn by the mother. The sensor design conforms to the distinctive features of the fetal heart tone, namely, the acoustic signature, frequency spectrum, signal amplitude, and localization. The components of a sensor serve to fulfill five functions: signal detection, acceleration cancellation, acoustical isolation, electrical shielding, and electrical isolation of the mother. A theoretical analysis of the sensor response yields a numerical value for the sensor sensitivity, which is compared to experiment in an in vitro sensor calibration. Finally, an in vivo test on patients within the last six weeks of term reveals that nonstress test recordings from the acoustic monitor compare well with those obtained from conventional ultrasound.

  8. Should we really avoid giving oxygen to mothers with concerning fetal heart rate patterns?

    PubMed

    Garite, Thomas J; Nageotte, Michael P; Parer, Julian T

    2015-04-01

    We challenge a provocative article entitled "Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful" by Hamel et al in the August issue of the Journal. The authors contend there is no good evidence that oxygen administration to the mother of a fetus with a concerning fetal heart rate pattern prevents acidosis and that in theory such oxygen administration may actually or potentially do harm to the fetus. It is clear that oxygen is administered quite often to women in labor, especially to those with category II fetal heart rate patterns and, because more than 80% of women in labor have these patterns and the majority of these patterns are unlikely to be associated with significant fetal hypoxia, that such oxygen administration is greatly overused. We describe in this article evidence that oxygen given to the mother actually does improve fetal oxygenation, especially in hypoxemic fetuses, and make arguments that there really is no substantial evidence that, except in theory, maternal oxygen administration causes any harm to the fetus. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Special Tests for Monitoring Fetal Health

    MedlinePlus

    ... a nonstress test? The nonstress test measures the fetal heart rate in response to fetal movement over time. The ... A belt with a sensor that measures the fetal heart rate is placed around your abdomen. The fetal heart ...

  10. Prenatally diagnosed fetal lung lesions with associated conotruncal heart defects: is there a genetic association?

    PubMed

    Hüsler, Margaret R; Wilson, R Douglas; Rychik, Jack; Bebbington, Michael W; Johnson, Mark P; Mann, Stephanie E; Hedrick, Holly L; Adzick, Scott

    2007-12-01

    Congenital lung malformation can easily be diagnosed by prenatal ultrasound. Associated extrapulmonary malformations such as heart defects and chromosomal aberrations are rare. The objective of this study was to describe the natural history, outcome and other associated malformations in fetuses with lung lesions and an associated heart defect. Retrospective analysis of 4 cases of prenatally diagnosed fetal CCAMs and hybrid lesions with an associated heart defect and review of 8 cases in the literature. At a single referral center 1.9% of the fetuses with Congenital cystic adenomatoid malformation (CCAM) were diagnosed with an associated heart defect. Seven of the total 12 cases (58%) reviewed had a conotruncal heart abnormality. Chromosomal abnormalities were found in 5 (42%) of the cases. This retrospective review shows that karyotyping in fetal lung lesions with an associated heart defect or isolated large lung lesions is indicated. It also suggests that there is a subpopulation of fetuses with CCAMs who have conotruncal heart defects. This finding may suggest a common genetic background. Copyright (c) 2007 John Wiley & Sons, Ltd.

  11. Transabdominal recordings of fetal heart rate in extremely small fetuses.

    PubMed

    Odendaal, Hein; Groenewald, Coen; Hankins, Gary D V; du Plessis, Carlie; Myers, Michael M; Fifer, William P

    2017-11-12

    As part of the fetal assessment for the Safe Passage Study, we recorded raw data of the fetal ECG via five maternal abdominal wall electrodes from 20 weeks to 23 weeks 6 days' gestation. For this study were extracted and analyzed the FHR patterns from the stored raw data in 16 stillbirths where the fetus weighed less than 1000 g and where autopsy was performed. Birth weights ranged from 190 to 970 g. The proportion FHR signal loss ranged from 0.3% to 21.1%. In the smallest fetus the heart weighed 1.3 g, yet the FHR signal loss was only 0.9%.

  12. Fetal myosin immunoreactivity in human dystrophic muscle.

    PubMed

    Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S

    1986-01-01

    We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

  13. Monitoring fetal heart rate during pregnancy: contributions from advanced signal processing and wearable technology.

    PubMed

    Signorini, Maria G; Fanelli, Andrea; Magenes, Giovanni

    2014-01-01

    Monitoring procedures are the basis to evaluate the clinical state of patients and to assess changes in their conditions, thus providing necessary interventions in time. Both these two objectives can be achieved by integrating technological development with methodological tools, thus allowing accurate classification and extraction of useful diagnostic information. The paper is focused on monitoring procedures applied to fetal heart rate variability (FHRV) signals, collected during pregnancy, in order to assess fetal well-being. The use of linear time and frequency techniques as well as the computation of non linear indices can contribute to enhancing the diagnostic power and reliability of fetal monitoring. The paper shows how advanced signal processing approaches can contribute to developing new diagnostic and classification indices. Their usefulness is evaluated by comparing two selected populations: normal fetuses and intra uterine growth restricted (IUGR) fetuses. Results show that the computation of different indices on FHRV signals, either linear and nonlinear, gives helpful indications to describe pathophysiological mechanisms involved in the cardiovascular and neural system controlling the fetal heart. As a further contribution, the paper briefly describes how the introduction of wearable systems for fetal ECG recording could provide new technological solutions improving the quality and usability of prenatal monitoring.

  14. The electrical heart axis and ST events in fetal monitoring: A post-hoc analysis following a multicentre randomised controlled trial.

    PubMed

    Vullings, Rik; Verdurmen, Kim M J; Hulsenboom, Alexandra D J; Scheffer, Stephanie; de Lau, Hinke; Kwee, Anneke; Wijn, Pieter F F; Amer-Wåhlin, Isis; van Laar, Judith O E H; Oei, S Guid

    2017-01-01

    Reducing perinatal morbidity and mortality is one of the major challenges in modern health care. Analysing the ST segment of the fetal electrocardiogram was thought to be the breakthrough in fetal monitoring during labour. However, its implementation in clinical practice yields many false alarms and ST monitoring is highly dependent on cardiotocogram assessment, limiting its value for the prediction of fetal distress during labour. This study aims to evaluate the relation between physiological variations in the orientation of the fetal electrical heart axis and the occurrence of ST events. A post-hoc analysis was performed following a multicentre randomised controlled trial, including 1097 patients from two participating centres. All women were monitored with ST analysis during labour. Cases of fetal metabolic acidosis, poor signal quality, missing blood gas analysis, and congenital heart disease were excluded. The orientation of the fetal electrical heart axis affects the height of the initial T/QRS baseline, and therefore the incidence of ST events. We grouped tracings with the same initial baseline T/QRS value. We depicted the number of ST events as a function of the initial baseline T/QRS value with a linear regression model. A significant increment of ST events was observed with increasing height of the initial T/QRS baseline, irrespective of the fetal condition; correlation coefficient 0.63, p<0.001. The most frequent T/QRS baseline is 0.12. The orientation of the fetal electrical heart axis and accordingly the height of the initial T/QRS baseline should be taken into account in fetal monitoring with ST analysis.

  15. Intrapartum fetal heart rate classification from trajectory in Sparse SVM feature space.

    PubMed

    Spilka, J; Frecon, J; Leonarduzzi, R; Pustelnik, N; Abry, P; Doret, M

    2015-01-01

    Intrapartum fetal heart rate (FHR) constitutes a prominent source of information for the assessment of fetal reactions to stress events during delivery. Yet, early detection of fetal acidosis remains a challenging signal processing task. The originality of the present contribution are three-fold: multiscale representations and wavelet leader based multifractal analysis are used to quantify FHR variability ; Supervised classification is achieved by means of Sparse-SVM that aim jointly to achieve optimal detection performance and to select relevant features in a multivariate setting ; Trajectories in the feature space accounting for the evolution along time of features while labor progresses are involved in the construction of indices quantifying fetal health. The classification performance permitted by this combination of tools are quantified on a intrapartum FHR large database (≃ 1250 subjects) collected at a French academic public hospital.

  16. Parasympathetic tone variations according to umbilical cord pH at birth: a computerized fetal heart rate variability analysis.

    PubMed

    Butruille, Laura; De Jonckheere, Julien; Flocteil, Mathilde; Garabedian, Charles; Houfflin-Debarge, Véronique; Storme, Laurent; Deruelle, Philippe; Logier, Régis

    2017-12-01

    Non-reassuring fetal heart rate tracings reflect an imbalance between the parasympathetic and sympathetic nervous systems. In this situation, fetal asphyxia can be suspected and may be confirmed by metabolic measurements at birth like low pH or high base deficit values. The objective of this study was to determine whether fetal asphyxia during labor is related to parasympathetic nervous system activity. This is a retrospective study of a database collected in 5 centers. Two hundred and ninety-nine fetal heart rate tracings collected during labor were analyzed. Autonomic nervous system, especially the parasympathetic nervous system, was analyzed using an original index: the FSI (Fetal Stress Index). The FSI is a parasympathetic activity evaluation based on fetal heart rate variability analysis. Infants were grouped based on normal or low pH value at birth. FSI was measured during the last 30 min of labor before birth and compared between groups. The minimum value of the FSI during the last 30 min before delivery was significantly lower in the group with the lower umbilical cord arterial pH value. In this pilot study during labor, FSI was lower in the group of infants with low arterial pH at birth.

  17. Fetal heart rate and motor activity associations with maternal organochlorine levels: Results of an exploratory study

    PubMed Central

    DiPietro, Janet A.; Davis, Meghan F.; Costigan, Kathleen A; Barr, Dana Boyd

    2015-01-01

    Contemporaneous associations between circulating maternal organochlorines and measures of fetal heart rate and motor activity were evaluated. A panel of 47 organochlorines (OCs), including pesticides and polychlorinated biphenyls (PCBs), was analyzed from serum of 50 pregnant women at 36 weeks gestation. Data were empirically reduced into four factors and six individual compounds. All participants had detectable concentrations of at least one-quarter of the assayed OCs and, in general, higher socioeconomic level was associated with higher OC concentrations. Fetal heart rate measures were not consistently associated with maternal OCs. In contrast, one or more indicators of greater fetal motor activity were significantly associated with higher levels of the DDT and low chlorinated OC factors and five of the six individual compounds (heptachlor epoxide, trans nonachlor, oxychlordane, and PCBs 18 and 52). This preliminary demonstration of associations between fetal motor activity and maternal concentrations of persistent and pervasive environmental contaminants suggests that fetal assessment may be useful in ascertaining the potential early effects of these compounds on development. PMID:23591698

  18. Does gender of the fetus have any relation with fetal heart monitoring during the first and second stage of labor?

    PubMed

    Yohai, David; Baumfeld, Yael; Zilberstein, Tali; Yaniv Salem, Shimrit; Elharar, Debbie; Idan, Inbal; Mastrolia, Salvatore Andrea; Sheiner, Eyal

    2017-01-01

    To investigate fetal gender and its influences on neonatal outcomes, taking into consideration the available tools for the assessment of fetal well-being. We conducted a retrospective study comparing maternal, fetal and neonatal outcomes according to fetal gender, in women carrying a singleton gestation. A multivariate analysis was performed for the prediction of adverse neonatal outcomes according to fetal gender, after adjustment for gestational age, maternal age and fetal weight. A total of 682 pregnancies were included in the study, of them 56% (n = 383) were carrying a male fetus and 44% (n = 299) a females fetus. Male gender was associated with a significant higher rate of abnormal fetal heart tracing patterns during the first (67.7% versus 55.1, p = 0.001) and the second stage (77.6 versus 67.7, p = 0.01) of labor. Male gender was also significantly associated with lower Apgar scores at 1' (19.1% versus 10.7%, p < 0.01), as well as lower pH values (7.18 ± 0.15 versus 7.23 ± 0.18, p < 0.001), and significant differences in cord blood components (PCO 2 , PO 2 ) compared with female fetuses. In the multivariate analysis, male gender was found to be significantly associated with first (OR 1.76, 95% CI 1.28-2.43, p = 0.001) and second stage (OR 1.73, 95% CI 1.20-2.50, p < 0.01) pathological fetal heart tracing patterns, pH < 7.1, and for Apgar scores at 1'< 7. The present study confirms the general trend of a lower clinical performance of male neonates compared with females. In addition, the relation between fetal heart rate patterns during all stages of labor and fetal gender showed an independent association between male fetal gender and abnormal fetal heart monitoring during labor.

  19. Epigenomic Landscape of Human Fetal Brain, Heart, and Liver.

    PubMed

    Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

    2016-02-26

    The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Intra- and interobserver agreement among obstetric experts in court regarding the review of abnormal fetal heart rate tracings and obstetrical management.

    PubMed

    Sabiani, Laura; Le Dû, Renaud; Loundou, Anderson; d'Ercole, Claude; Bretelle, Florence; Boubli, Léon; Carcopino, Xavier

    2015-12-01

    The objective of the study was to evaluate the intra- and interobserver agreement among obstetric experts in court regarding the retrospective review of abnormal fetal heart rate tracings and obstetrical management of patients with abnormal fetal heart rate during labor. A total of 22 French obstetric experts in court reviewed 30 cases of term deliveries of singleton pregnancies diagnosed with at least 1 hour of abnormal fetal heart rate, including 10 cases with adverse neonatal outcome. The experts reviewed all cases twice within a 3-month interval, with the first review being blinded to neonatal outcome. For each case reviewed, the experts were provided with the obstetric data and copies of the complete fetal heart rate recording and the partogram. The experts were asked to classify the abnormal fetal heart rate tracing and to express whether they agreed with the obstetrical management performed. When they disagreed, the experts were asked whether they concluded that an error had been made and whether they considered the obstetrical management as the cause of cerebral palsy in children if any. Compared with blinded review, the experts were significantly more likely to agree with the obstetric management performed (P < .001) and with the mode of delivery (P < .001) when informed about the neonatal outcome and were less likely to conclude that an error had been made (P < .001) or to establish a link with potential cerebral palsy (P = .003). The experts' intraobserver agreement for the review of abnormal fetal heart rate tracing and obstetrical management were both mediocre (kappa = 0.46-0.51 and kappa = 0.48-0.53, respectively). The interobserver agreement for the review of abnormal fetal heart rate tracing was low and was not improved by knowledge of the neonatal outcome (kappa = 0.11-0.18). The interobserver agreement for the interpretation of obstetrical management was also low (kappa = 0.08-0.19) but appeared to be improved by knowledge of the neonatal outcome

  1. Fetal heart rate intermittency

    NASA Astrophysics Data System (ADS)

    Yum, Myung-Kul; Kim, Jong-Hwa; Kim, Kyungsik

    2003-03-01

    We noticed that fetal heart rates(FHR) of immature fetuses intermittently showed unstable falls below baseline FHR which do not occur in mature fetuses. We aim to investigate the nature and maturational changes of intermittency of the FHR in normal fetuses, and to present the intermittency values of normal fetuses according to gestational weeks. FHR data of 450 normal fetuses between 23 and 40 weeks of gestation were studied. We performed multifractal analysis and calcualted a intermittency (C_1). The C1 values exhibited a strong negative linear correlation(P=0.0001) with the gestational weeks. At 27-28, 29-30, 33-34, and 37-38 gestational weeks, the C1 values were significantly lower than those of the previous two or four gestational weeks. The maturation of normal fetuses is related to decreasing the severity of the unstable falls in FHR that is measured by C_1, the intermittency. The C1 values according to the gestational weeks we presented can be used as credible values when estimating the degree of maturity of certain FHR.

  2. Establishment and characterization of the reversibly immortalized mouse fetal heart progenitors.

    PubMed

    Li, Mi; Chen, Yuan; Bi, Yang; Jiang, Wei; Luo, Qing; He, Yun; Su, Yuxi; Liu, Xing; Cui, Jing; Zhang, Wenwen; Li, Ruidong; Kong, Yuhan; Zhang, Jiye; Wang, Jinhua; Zhang, Hongyu; Shui, Wei; Wu, Ningning; Zhu, Jing; Tian, Jie; Yi, Qi-Jian; Luu, Hue H; Haydon, Rex C; He, Tong-Chuan; Zhu, Gao-Hui

    2013-01-01

    Progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart. Although cardiomyogenic differentiation has been reported for a variety of progenitor cell types, the biological factors that regulate effective cardiomyogenesis remain largely undefined. Primary cardiomyogenic progenitors (CPs) have a limited life span in culture, hampering the CPs' in vitro and in vivo studies. The objective of this study is to investigate if primary CPs isolated from fetal mouse heart can be reversibly immortalized with SV40 large T and maintain long-term cell proliferation without compromising cardiomyogenic differentiation potential. Primary cardiomyocytes were isolated from mouse E15.5 fetal heart, and immortalized retrovirally with the expression of SV40 large T antigen flanked with loxP sites. Expression of cardiomyogenic markers were determined by quantitative RT-PCR and immunofluorescence staining. The immortalization phenotype was reversed by using an adenovirus-mediated expression of the Cre reconbinase. Cardiomyogenic differentiation induced by retinoids or dexamethasone was assessed by an α-myosin heavy chain (MyHC) promoter-driven reporter. We demonstrate that the CPs derived from mouse E15.5 fetal heart can be efficiently immortalized by SV40 T antigen. The conditionally immortalized CPs (iCP15 clones) exhibit an increased proliferative activity and are able to maintain long-term proliferation, which can be reversed by Cre recombinase. The iCP15 cells express cardiomyogenic markers and retain differentiation potential as they can undergo terminal differentiate into cardiomyctes under appropriate differentiation conditions although the iCP15 clones represent a large repertoire of CPs at various differentiation stages. The removal of SV40 large T increases the iCPs' differentiation potential. Thus, the iCPs not only maintain long-term cell proliferative activity but also retain cardiomyogenic differentiation potential. Our results

  3. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

  4. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

  5. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

  6. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

  7. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

  8. Signal loss during fetal heart rate monitoring using maternal abdominal surface electrodes between 28 and 42 weeks of pregnancy.

    PubMed

    Fuchs, Tomasz; Pomorski, Michał; Grobelak, Krzysztof; Tomiałowicz, Marek; Zimmer, Mariusz

    2014-01-01

    Fetal electrocardiography is one of the methods for monitoring the well-being of the fetus. Signal loss limits the proper interpretation of electrocardiogram traces. The aim of this study was to assess the average signal loss in non-invasive abdominal fetal electrocardiogram (fECG) monitoring using the KOMPOREL fetal monitoring system (ITAM, Zabrze, Poland) in women between 28 and 42 week of pregnancy. The results were compared to FIGO (International Federation of Gynaecology and Obstetric) and DGGG (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e.V.) recommendations concerning fetal heart monitoring. The correlation between fetal ECG signal quality, week of pregnancy and patient BMI was evaluated. 773 pregnant women, hospitalized and diagnosed in the Department of Gynecology and Obstetrics, Wroclaw Medical University, underwent 30 min of abdominal fECG recordings using the KOMPOREL fetal monitoring system. The average signal loss in abdominal fECG monitoring in the study group was 32%. FIGO recommendations describe an acceptable fetal signal loss of 20%. In our study, 46% (357/773) of the recordings were up to FIGO standards, with fetal heart rate success rates above 80%. According to DGGG guidelines, with acceptable fetal signal loss of 15%, only 39% (303/773) of the recordings could be assessed as accurate. No correlation between fECG signal quality, week of pregnancy and patient BMI was proved. The average signal loss in abdominal fECG monitoring in our study group was 32%. Low fECG signal quality may constitute a potentially limiting factor of the described fetal heart monitoring system. No relationship between fECG signal quality, week of pregnancy and patient BMI was proved.

  9. Fetal and neonatal mortality in patients with isolated congenital heart diseases and heart conditions associated with extracardiac abnormalities.

    PubMed

    Marantz, Pablo; Sáenz Tejeira, M Mercedes; Peña, Gabriela; Segovia, Alejandra; Fustiñana, Carlos

    2013-10-01

    Congenital malformations are a known cause of intrauterine death; of them, congenital heart diseases (CHDs) are accountable for the highest fetal and neonatal mortality rates. They are strongly associated with other extracardiac malformations and an early fetal mortality. Two hundred and twenty fves cases of CHDs are presented. Of them, 155 were isolated CHDs (group A) and 70 were associated with extracardiac malformations, chromosomal disorders, or genetic syndromes (group B). The overall mortality in group B was higher than that observed in group A (p <0.01). Prenatal mortality was similar in both groups: A: 8.4% (13 out of 155); B: 15.7% (11 out of 70). Postnatal mortality was A: 16.8% (26 out of 155) (p <0.01), OR: 0.52 (95% CI: 0.16-1.7); B: 32.9% (23 out of 70) (p <0.01), OR: 0.41 (95% CI: 0.20-0.83). Heart diseases associated with extracardiac abnormalities had a higher mortality rate than isolated congenital heart diseases in the period up to 60 weeks of postmenstrual age (140 days post-term). No differences were observed between both groups of patients in terms of prenatal mortality.

  10. Complexity of heart rate fluctuations in near-term sheep and human fetuses during sleep.

    PubMed

    Frank, Birgit; Frasch, Martin G; Schneider, Uwe; Roedel, Marcus; Schwab, Matthias; Hoyer, Dirk

    2006-10-01

    We investigated how the complexity of fetal heart rate fluctuations (fHRF) is related to the sleep states in sheep and human fetuses. The complexity as a function of time scale for fetal heart rate data for 7 sheep and 27 human fetuses was estimated in rapid eye movement (REM) and non-REM sleep by means of permutation entropy and the associated Kullback-Leibler entropy. We found that in humans, fHRF complexity is higher in non-REM than REM sleep, whereas in sheep this relationship is reversed. To show this relation, choice of the appropriate time scale is crucial. In sheep fetuses, we found differences in the complexity of fHRF between REM and non-REM sleep only for larger time scales (above 2.5 s), whereas in human fetuses the complexity was clearly different between REM and non-REM sleep over the whole range of time scales. This may be due to inherent time scales of complexity, which reflect species-specific functions of the autonomic nervous system. Such differences have to be considered when animal data are translated to the human situation.

  11. Prone position craniotomy in pregnancy without fetal heart rate monitoring.

    PubMed

    Jacob, Jean; Alexander, Ashish; Philip, Shoba; Thomas, Anoop

    2016-09-01

    A pregnant patient in second trimester scheduled for posterior fossa craniotomy in prone position is a challenge for the anesthesiologist. Things to consider are physiological changes during pregnancy, non-obstetric surgery in pregnant patients, neuroanesthetic principles, effects of prone positioning, and need for fetal heart rate (FHR) monitoring. We have described the anesthetic management of this case and discussed intra-operative FHR monitoring including controversies about its role, indications, and various options available as per fetal gestational age. In our case we attempted intermittent intra-operative FHR monitoring to optimize maternal positioning and fetal oxygenation even though the fetus was pre-viable. However the attempt was abandoned due to practical difficulties with prone positioning. Patient made good neurological recovery following the procedure and delivered a healthy term baby 4 months later. Decisions regarding fetal monitoring should be individualized based on viability of the fetus and feasibility of emergency cesarean delivery. Good communication between a multidisciplinary team involving neurosurgeon, anesthesiologist, obstetrician, and neonatologist is important for a successful outcome for mother and fetus. We conclude that prone position neurosurgery can safely be carried out in a pregnant patient with pre-viable fetus without FHR monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow, Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

    PubMed Central

    2015-01-01

    Study Overview The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Conclusion and Significance Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system. PMID:25915506

  13. Gestational dietary protein is associated with sex specific decrease in blood flow, fetal heart growth and post-natal blood pressure of progeny.

    PubMed

    Hernandez-Medrano, Juan H; Copping, Katrina J; Hoare, Andrew; Wapanaar, Wendela; Grivell, Rosalie; Kuchel, Tim; Miguel-Pacheco, Giuliana; McMillen, I Caroline; Rodgers, Raymond J; Perry, Viv E A

    2015-01-01

    The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14 mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60 d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98 dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36 dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60 d up to 23 dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system.

  14. Intermittent auscultation (IA) of fetal heart rate in labour for fetal well-being.

    PubMed

    Martis, Ruth; Emilia, Ova; Nurdiati, Detty S; Brown, Julie

    2017-02-13

    The goal of fetal monitoring in labour is the early detection of a hypoxic baby. There are a variety of tools and methods available for intermittent auscultation (IA) of the fetal heart rate (FHR). Low- and middle-income countries usually have only access to a Pinard/Laënnec or the use of a hand-held Doppler device. Currently, there is no robust evidence to guide clinical practice on the most effective IA tool to use, timing intervals and length of listening to the fetal heart for women during established labour. To evaluate the effectiveness of different tools for IA of the fetal heart rate during labour including frequency and duration of auscultation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (19 September 2016), contacted experts and searched reference lists of retrieved articles. All published and unpublished randomised controlled trials (RCTs) or cluster-RCTs comparing different tools and methods used for intermittent fetal auscultation during labour for fetal and maternal well-being. Quasi-RCTs, and cross-over designs were not eligible for inclusion. All review authors independently assessed eligibility, extracted data and assessed risk of bias for each trial. Data were checked for accuracy. We included three studies (6241 women and 6241 babies), but only two studies are included in the meta-analyses (3242 women and 3242 babies). Both were judged as high risk for performance bias due to the inability to blind the participants and healthcare providers to the interventions. Evidence was graded as moderate to very low quality; the main reasons for downgrading were study design limitations and imprecision of effect estimates. Intermittent Electronic Fetal Monitoring (EFM) using Cardiotocography (CTG) with routine Pinard (one trial)There was no clear difference between groups in low Apgar scores at five minutes (reported as < six at five minutes after birth) (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.24 to 1.83, 633

  15. Incidence and predictors of obstetric and fetal complications in women with structural heart disease.

    PubMed

    van Hagen, Iris M; Roos-Hesselink, Jolien W; Donvito, Valentina; Liptai, Csilla; Morissens, Marielle; Murphy, Daniel J; Galian, Laura; Bazargani, Nooshin Mohd; Cornette, Jérôme; Hall, Roger; Johnson, Mark R

    2017-10-01

    Women with cardiac disease becoming pregnant have an increased risk of obstetric and fetal events. The aim of this study was to study the incidence of events, to validate the modified WHO (mWHO) risk classification and to search for event-specific predictors. The Registry Of Pregnancy And Cardiac disease is a worldwide ongoing prospective registry that has enrolled 2742 pregnancies in women with known cardiac disease (mainly congenital and valvular disease) before pregnancy, from January 2008 up to April 2014. Mean age was 28.2±5.5 years, 45% were nulliparous and 33.3% came from emerging countries. Obstetric events occurred in 231 pregnancies (8.4%). Fetal events occurred in 651 pregnancies (23.7%). The mWHO classification performed poorly in predicting obstetric (c-statistic=0.601) and fetal events (c-statistic=0.561). In multivariable analysis, aortic valve disease was associated with pre-eclampsia (OR=2.6, 95%CI=1.3 to 5.5). Congenital heart disease (CHD) was associated with spontaneous preterm birth (OR=1.8, 95%CI=1.2 to 2.7). Complex CHD was associated with small-for-gestational-age neonates (OR=2.3, 95%CI=1.5 to 3.5). Multiple gestation was the strongest predictor of fetal events: fetal/neonatal death (OR=6.4, 95%CI=2.5 to 16), spontaneous preterm birth (OR=5.3, 95%CI=2.5 to 11) and small-for-gestational age (OR=5.0, 95%CI=2.5 to 9.8). The mWHO classification is not suitable for prediction of obstetric and fetal events in women with cardiac disease. Maternal complex CHD was independently associated with fetal growth restriction and aortic valve disease with pre-eclampsia, potentially offering an insight into the pathophysiology of these pregnancy complications. The increased rates of adverse obstetric and fetal outcomes in women with pre-existing heart disease should be highlighted during counselling. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless

  16. Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

    PubMed

    Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

    2015-06-01

    Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by

  17. Variation of safety indices during in the learning curve for color Doppler assessment of the fetal heart at 11+0 to 13+6 weeks' gestation.

    PubMed

    Nemescu, Dragos; Berescu, Anca; Rotariu, Cristian

    2015-12-01

    The aim of our study was to analyze the variation of acoustic output, as expressed by the thermal (TI) and mechanical index (MI), during the learning curve for a fetal heart scan at 11-13 gestational weeks, with the introduction of a new ultrasound system. This was a prospective, observational study on 303 normal fetuses. The fetal heart was examined transabdominally using B-Mode and high definition (HD) color Doppler to obtain standard parameters: four-chamber, outflow tracts and three-vessel-trachea views. Data were analyzed in groups of 20 consecutive examinations and the percentage of successful examinations was calculated. TI and MI were retrieved from HD color Doppler examinations of the fetal heart and from pulsed-wave Doppler assessment of the tricuspid flow and ductus venosus. MI values from the color Doppler examination of the fetal heart showed a continuous decrease (0.81 to 0.75, p<0.001), along the learning phase. TI and MI indices from pulsed-wave Doppler evaluation of the tricuspid flow increased at the beginning of the learning phase and stabilized afterwards (0.34 to 0.36, p<0.05 and 0.37 to 0.4, p<0.001, respectively). TI from color Doppler exam of the heart and indices from ductus venosus assessment were very constant and did not change along the studied periods. The length of Doppler examination of the heart increased after about 80 cases by 25%, to a mean of 4 minutes (p<0.05). Safety indices from Doppler evaluation of the fetal heart and tricuspid flow vary during the learning curve for fetal heart assessment. Also, the occurrence of constant values suggests the potential for their supplementary active reduction. For a better adaptation to a new ultrasound technology, the sonographer should scan the fetal heart longer in the first trimester and follow displayed safety indices along the first 80 cases.

  18. Do spectral bands of fetal heart rate variability associate with concomitant fetal scalp pH?

    PubMed

    Siira, Saila M; Ojala, Tiina H; Vahlberg, Tero J; Rosén, Karl G; Ekholm, Eeva M

    2013-09-01

    Objective information on specific fetal heart rate (FHR) parameters would be advantageous when assessing fetal responses to hypoxia. Small, visually undetectable changes in FHR variability can be quantified by power spectral analysis of FHR variability. To investigate the effect of intrapartum hypoxia and acidemia on spectral powers of FHR variability. This is a retrospective observational clinical study with data from an EU multicenter project. We had 462 fetuses with a normal pH-value (pH>7.20; controls) in fetal scalp blood sample (FBS) and 81 fetuses with a low scalp pH-value (≤ 7.20; low-FBS pH-fetuses). The low-FBS pH-fetuses were further divided into two subgroups according to the degree of acidemia: fetuses with FBS pH7.11-7.20 (n = 58) and fetuses with FBS pH ≤7.10 (n = 23). Spectral powers of FHR variability in relation to the concomitant FBS pH-value. Fetuses with FBS pH ≤7.20 had increased spectral powers of FHR variability compared with controls (2.49 AU vs. 2.23 AU; p = 0.038). However, the subgroup of most affected fetuses (those with FBS pH ≤7.10) had significantly lower FHR variability spectral powers when compared to fetuses with FBS pH7.11-7.20. This study shows that spectral powers of FHR variability change as a fetus becomes hypoxic, and that spectral powers decrease with deepening fetal acidemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Using uterine activity to improve fetal heart rate variability analysis for detection of asphyxia during labor.

    PubMed

    Warmerdam, G J J; Vullings, R; Van Laar, J O E H; Van der Hout-Van der Jagt, M B; Bergmans, J W M; Schmitt, L; Oei, S G

    2016-03-01

    During labor, uterine contractions can cause temporary oxygen deficiency for the fetus. In case of severe and prolonged oxygen deficiency this can lead to asphyxia. The currently used technique for detection of asphyxia, cardiotocography (CTG), suffers from a low specificity. Recent studies suggest that analysis of fetal heart rate variability (HRV) in addition to CTG can provide information on fetal distress. However, interpretation of fetal HRV during labor is difficult due to the influence of uterine contractions on fetal HRV. The aim of this study is therefore to investigate whether HRV features differ during contraction and rest periods, and whether these differences can improve the detection of asphyxia. To this end, a case-control study was performed, using 14 cases with asphyxia that were matched with 14 healthy fetuses. We did not find significant differences for individual HRV features when calculated over the fetal heart rate without separating contractions and rest periods (p  >  0.30 for all HRV features). Separating contractions from rest periods did result in a significant difference. In particular the ratio between HRV features calculated during and outside contractions can improve discrimination between fetuses with and without asphyxia (p  <  0.04 for three out of four ratio HRV features that were studied in this paper).

  20. Fetal heart rate monitoring device using condenser microphone sensor: Validation and comparison to standard devices.

    PubMed

    Ahmad, Husna Azyan Binti; El-Badawy, Ismail M; Singh, Om Prakash; Hisham, Rozana Binti; Malarvili, M B

    2018-04-27

    Fetal heart rate (FHR) monitoring device is highly demanded to assess the fetus health condition in home environments. Conventional standard devices such as ultrasonography and cardiotocography are expensive, bulky and uncomfortable and consequently not suitable for long-term monitoring. Herein, we report a device that can be used to measure fetal heart rate in clinical and home environments. The proposed device measures and displays the FHR on a screen liquid crystal display (LCD). The device consists of hardware that comprises condenser microphone sensor, signal conditioning, microcontroller and LCD, and software that involves the algorithm used for processing the conditioned fetal heart signal prior to FHR display. The device's performance is validated based on analysis of variance (ANOVA) test. FHR data was recorded from 22 pregnant women during the 17th to 37th week of gestation using the developed device and two standard devices; AngelSounds and Electronic Stethoscope. The results show that F-value (1.5) is less than F, (3.1) and p-value (p> 0.05). Accordingly, there is no significant difference between the mean readings of the developed and existing devices. Hence, the developed device can be used for monitoring FHR in clinical and home environments.

  1. Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace.

    PubMed

    East, Christine E; Leader, Leo R; Sheehan, Penelope; Henshall, Naomi E; Colditz, Paul B; Lau, Rosalind

    2015-05-01

    Fetal scalp blood sampling for lactate estimation may be considered following identification of an abnormal or non-reassuring fetal heart rate pattern. The smaller volume of blood required for this test, compared with the more traditional pH estimation, may improve sampling rates. The appropriate use of this practice mandates systematic review of its safety and clinical effectiveness prior to widespread introduction. To evaluate the effectiveness and risks of fetal scalp lactate sampling in the assessment of fetal well-being during labour, compared with no testing or alternative testing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015). All published and unpublished randomised and quasi-randomised trials that compared fetal scalp lactate testing with no testing or alternative testing to evaluate fetal status in the presence of a non-reassuring cardiotocograph during labour. We used the standard methodological procedures of the Cochrane Pregnancy and Childbirth Group. Two review authors independently assessed the studies. The search identified two completed randomised controlled trials (RCTs) and two ongoing trials. The two published RCTs considered outcomes for 3348 mother-baby pairs allocated to either lactate or pH estimation of fetal blood samples when clinically indicated in labour. Overall, the published RCTs were of low or unclear risk of bias. There was a high risk of performance bias, because it would not have been feasible to blind clinicians or participants.No statistically significant between-group differences were found for neonatal encephalopathy (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.32 to 3.09, one study, 2992 infants) or death. No studies reported neonatal seizures. We had planned to report death with other morbidities, for example, neonatal encephalopathy; however, the data were not available in a format suitable for this, therefore death due to congenital abnormality was considered alone

  2. Cross-hemispheric functional connectivity in the human fetal brain.

    PubMed

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  3. Misidentification of maternal heart rate as fetal on cardiotocography during the second stage of labor: the role of the fetal electrocardiograph.

    PubMed

    Nurani, Raisha; Chandraharan, Edwin; Lowe, Virginia; Ugwumadu, Austin; Arulkumaran, Sabaratnam

    2012-12-01

    To identify the incidence of fetal heart rate (FHR) accelerations in the second stage of labor and the role of fetal electrocardiograph (ECG) in avoiding misidentification of maternal heart rate (MHR) as FHR. Retrospective observational study. University hospital labor ward, London, UK. Cardiotocograph (CTG) tracings of 100 fetuses monitored using external transducers and internal scalp electrodes. CTG traces that fulfilled inclusion criteria were selected from an electronic FHR monitoring database. Rate of accelerations during external and internal monitoring as well as decelerations for a period of 60 minutes prior to delivery were determined. The role of fetal ECG in differentiating between MHR and FHR trace was explored. Decelerations occurred in 89% of CTG traces during the second stage of labor. Accelerations indicating possible recording of FHR or MHR were found in 28.1 and 10.9% of cases recorded by an external ultrasound transducer as well as internal scalp electrode, respectively. Accelerations coinciding with uterine contractions occurred only in 11.7 and 4% of external and internal recording of FHR, respectively. Absence of 'p-wave' of the ECG waveform was associated with MHR trace. Decelerations were the commonest CTG feature during the second stage of labor. The incidence of accelerations coinciding with uterine contractions was less than half in fetuses monitored using a fetal scalp electrode. Analysing the ECG waveform for the absence of 'p-wave' helps in differentiating MHR from FHR. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. Outcome in early-onset fetal growth restriction is best combining computerized fetal heart rate analysis with ductus venosus Doppler: insights from the Trial of Umbilical and Fetal Flow in Europe.

    PubMed

    Frusca, Tiziana; Todros, Tullia; Lees, Christoph; Bilardo, Caterina M

    2018-02-01

    Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02-1.52) and infant survival without neurodevelopmental impairment at 2

  5. Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

    PubMed Central

    Thompson, Loren P.; Liu, Hongshan; Evans, LaShauna; Mong, Jessica A.

    2011-01-01

    This study tested the hypothesis that maternal nicotine ingestion increases matrix metalloproteinase (MMP) expression in fetal hearts, which is mediated by the generation of reactive oxygen species. Timed pregnant guinea pigs were administered either water alone, nicotine (200 μg/mL), N-acetylcysteine (NAC), or nicotine plus NAC in their drinking water for 10 days at 52-day gestation (term = 65 days). Near-term (62 days), anesthetized fetuses were extracted, hearts were excised, and left cardiac ventricles snap frozen for analysis of MMP-2/-9/-13 protein and activity levels. Interstitial collagens were identified by Picrosirius red stain to assess changes in the extracellular matrix. Prenatal nicotine increased active MMP-2 forms and interstitial collagen but had no effect on either pro- or active MMP-9 or MMP-13 forms. In the presence of nicotine, NAC decreased active MMP-2 protein levels and reversed the nicotine-induced increase in collagen staining. We conclude that prenatal nicotine alters MMP-2 expression in fetal hearts that may be mediated by reactive oxygen species generation. PMID:21775771

  6. A prospective cohort study of fetal heart rate monitoring: deceleration area is predictive of fetal acidemia.

    PubMed

    Cahill, Alison G; Tuuli, Methodius G; Stout, Molly J; López, Julia D; Macones, George A

    2018-05-01

    Intrapartum electronic fetal monitoring is the most commonly used tool in obstetrics in the United States; however, which electronic fetal monitoring patterns predict acidemia remains unclear. This study was designed to describe the frequency of patterns seen in labor using modern nomenclature, and to test the hypothesis that visually interpreted patterns are associated with acidemia and morbidities in term infants. We further identified patterns prior to delivery, alone or in combination, predictive of acidemia and neonatal morbidity. This was a prospective cohort study of 8580 women from 2010 through 2015. Patients were all consecutive women laboring at ≥37 weeks' gestation with a singleton cephalic fetus. Electronic fetal monitoring patterns during the 120 minutes prior to delivery were interpreted in 10-minute epochs. Interpretation included the category system and individual electronic fetal monitoring patterns per the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria as well as novel patterns. The primary outcome was fetal acidemia (umbilical artery pH ≤7.10); neonatal morbidities were also assessed. Final regression models for acidemia adjusted for nulliparity, pregestational diabetes, and advanced maternal age. Area under the receiver operating characteristic curves were used to assess the test characteristics of individual models for acidemia and neonatal morbidity. Of 8580 women, 149 (1.7%) delivered acidemic infants. Composite neonatal morbidity was diagnosed in 757 (8.8%) neonates within the total cohort. Persistent category I, and 10-minute period of category III, were significantly associated with normal pH and acidemia, respectively. Total deceleration area was most discriminative of acidemia (area under the receiver operating characteristic curves, 0.76; 95% confidence interval, 0.72-0.80), and deceleration area with any 10 minutes of tachycardia had the greatest discriminative ability for neonatal

  7. A Phonocardiographic-Based Fiber-Optic Sensor and Adaptive Filtering System for Noninvasive Continuous Fetal Heart Rate Monitoring.

    PubMed

    Martinek, Radek; Nedoma, Jan; Fajkus, Marcel; Kahankova, Radana; Konecny, Jaromir; Janku, Petr; Kepak, Stanislav; Bilik, Petr; Nazeran, Homer

    2017-04-18

    This paper focuses on the design, realization, and verification of a novel phonocardiographic- based fiber-optic sensor and adaptive signal processing system for noninvasive continuous fetal heart rate (fHR) monitoring. Our proposed system utilizes two Mach-Zehnder interferometeric sensors. Based on the analysis of real measurement data, we developed a simplified dynamic model for the generation and distribution of heart sounds throughout the human body. Building on this signal model, we then designed, implemented, and verified our adaptive signal processing system by implementing two stochastic gradient-based algorithms: the Least Mean Square Algorithm (LMS), and the Normalized Least Mean Square (NLMS) Algorithm. With this system we were able to extract the fHR information from high quality fetal phonocardiograms (fPCGs), filtered from abdominal maternal phonocardiograms (mPCGs) by performing fPCG signal peak detection. Common signal processing methods such as linear filtering, signal subtraction, and others could not be used for this purpose as fPCG and mPCG signals share overlapping frequency spectra. The performance of the adaptive system was evaluated by using both qualitative (gynecological studies) and quantitative measures such as: Signal-to-Noise Ratio-SNR, Root Mean Square Error-RMSE, Sensitivity-S+, and Positive Predictive Value-PPV.

  8. A Phonocardiographic-Based Fiber-Optic Sensor and Adaptive Filtering System for Noninvasive Continuous Fetal Heart Rate Monitoring

    PubMed Central

    Martinek, Radek; Nedoma, Jan; Fajkus, Marcel; Kahankova, Radana; Konecny, Jaromir; Janku, Petr; Kepak, Stanislav; Bilik, Petr; Nazeran, Homer

    2017-01-01

    This paper focuses on the design, realization, and verification of a novel phonocardiographic- based fiber-optic sensor and adaptive signal processing system for noninvasive continuous fetal heart rate (fHR) monitoring. Our proposed system utilizes two Mach-Zehnder interferometeric sensors. Based on the analysis of real measurement data, we developed a simplified dynamic model for the generation and distribution of heart sounds throughout the human body. Building on this signal model, we then designed, implemented, and verified our adaptive signal processing system by implementing two stochastic gradient-based algorithms: the Least Mean Square Algorithm (LMS), and the Normalized Least Mean Square (NLMS) Algorithm. With this system we were able to extract the fHR information from high quality fetal phonocardiograms (fPCGs), filtered from abdominal maternal phonocardiograms (mPCGs) by performing fPCG signal peak detection. Common signal processing methods such as linear filtering, signal subtraction, and others could not be used for this purpose as fPCG and mPCG signals share overlapping frequency spectra. The performance of the adaptive system was evaluated by using both qualitative (gynecological studies) and quantitative measures such as: Signal-to-Noise Ratio—SNR, Root Mean Square Error—RMSE, Sensitivity—S+, and Positive Predictive Value—PPV. PMID:28420215

  9. QRS classification and spatial combination for robust heart rate detection in low-quality fetal ECG recordings.

    PubMed

    Warmerdam, G; Vullings, R; Van Pul, C; Andriessen, P; Oei, S G; Wijn, P

    2013-01-01

    Non-invasive fetal electrocardiography (ECG) can be used for prolonged monitoring of the fetal heart rate (FHR). However, the signal-to-noise-ratio (SNR) of non-invasive ECG recordings is often insufficient for reliable detection of the FHR. To overcome this problem, source separation techniques can be used to enhance the fetal ECG. This study uses a physiology-based source separation (PBSS) technique that has already been demonstrated to outperform widely used blind source separation techniques. Despite the relatively good performance of PBSS in enhancing the fetal ECG, PBSS is still susceptible to artifacts. In this study an augmented PBSS technique is developed to reduce the influence of artifacts. The performance of the developed method is compared to PBSS on multi-channel non-invasive fetal ECG recordings. Based on this comparison, the developed method is shown to outperform PBSS for the enhancement of the fetal ECG.

  10. Stochastic time series analysis of fetal heart-rate variability

    NASA Astrophysics Data System (ADS)

    Shariati, M. A.; Dripps, J. H.

    1990-06-01

    Fetal Heart Rate(FHR) is one of the important features of fetal biophysical activity and its long term monitoring is used for the antepartum(period of pregnancy before labour) assessment of fetal well being. But as yet no successful method has been proposed to quantitatively represent variety of random non-white patterns seen in FHR. Objective of this paper is to address this issue. In this study the Box-Jenkins method of model identification and diagnostic checking was used on phonocardiographic derived FHR(averaged) time series. Models remained exclusively autoregressive(AR). Kalman filtering in conjunction with maximum likelihood estimation technique forms the parametric estimator. Diagnosrics perfonned on the residuals indicated that a second order model may be adequate in capturing type of variability observed in 1 up to 2 mm data windows of FHR. The scheme may be viewed as a means of data reduction of a highly redundant information source. This allows a much more efficient transmission of FHR information from remote locations to places with facilities and expertise for doser analysis. The extracted parameters is aimed to reflect numerically the important FHR features. These are normally picked up visually by experts for their assessments. As a result long term FHR recorded during antepartum period could then be screened quantitatively for detection of patterns considered normal or abnonnal. 1.

  11. Internal fetal monitoring (image)

    MedlinePlus

    Internal fetal monitoring involves placing a electrode directly on the fetal scalp through the cervix. This test is performed to evaluate fetal heart rate and variability between beats, especially ...

  12. Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart

    PubMed Central

    Wang, Jingying; Ma, Heng; Tong, Chao; Zhang, Hanying; Lawlis, Gavin B.; Li, Yuanda; Zang, Mengwei; Ren, Jun; Nijland, Mark J.; Ford, Stephen P.; Nathanielsz, Peter W.; Li, Ji

    2010-01-01

    Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well-established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were increased (P<0.01, n=8) in OB (35.09±2.03 mg/dl and 3.40±1.43 μU/ml, respectively) vs. CON ewes (23.80±1.38 mg/dl and 0.769±0.256 μU/ml). Phosphorylation of AMP-activated protein kinase (AMPK), a cardioprotective signaling pathway, was reduced (P<0.05), while the stress signaling pathway, p38 MAPK, was up-regulated (P<0.05) in OB maternal and fetal hearts. Phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) at Ser-307 were increased (P<0.05) in OB fetal heart associated with lower downstream PI3K-Akt activity (P<0.05), indicating impaired cardiac insulin signaling. Although OB fetal hearts exhibited a normal contractile function vs. CON fetal hearts during basal perfusion, they developed an impaired heart-rate-left-ventricular-developed pressure product in response to high workload stress. Taken together, fetuses of OB mothers demonstrate alterations in cardiac PI3K-Akt, AMPK, and JNK-IRS-1 signaling pathways that would predispose them to insulin resistance and cardiac dysfunction.—Wang, J., Ma, H., Tong, C., Zhang, H., Lawlis, G. B., Li, Y., Zang, M., Ren, J., Nijland, M. J., Ford, S. P., Nathanielsz, P. W., Li, J. Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart. PMID:20110268

  13. Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

    NASA Astrophysics Data System (ADS)

    Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

    1988-11-01

    Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

  14. Global transcriptional profiling reveals similarities and differences between human stem cell-derived cardiomyocyte clusters and heart tissue.

    PubMed

    Synnergren, Jane; Améen, Caroline; Jansson, Andreas; Sartipy, Peter

    2012-02-27

    It is now well documented that human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes. These cells constitute a promising source of material for use in drug development, toxicity testing, and regenerative medicine. To assess their utility as replacement or complement to existing models, extensive phenotypic characterization of the cells is required. In the present study, we used microarrays and analyzed the global transcription of hESC-derived cardiomyocyte clusters (CMCs) and determined similarities as well as differences compared with reference samples from fetal and adult heart tissue. In addition, we performed a focused analysis of the expression of cardiac ion channels and genes involved in the Ca(2+)-handling machinery, which in previous studies have been shown to be immature in stem cell-derived cardiomyocytes. Our results show that hESC-derived CMCs, on a global level, have a highly similar gene expression profile compared with human heart tissue, and their transcriptional phenotype was more similar to fetal than to adult heart. Despite the high similarity to heart tissue, a number of significantly differentially expressed genes were identified, providing some clues toward understanding the molecular difference between in vivo sourced tissue and stem cell derivatives generated in vitro. Interestingly, some of the cardiac-related ion channels and Ca(2+)-handling genes showed differential expression between the CMCs and heart tissues. These genes may represent candidates for future genetic engineering to create hESC-derived CMCs that better mimic the phenotype of the cardiomyocytes present in the adult human heart.

  15. Fetal Heart Rate Monitoring during Labor

    MedlinePlus

    ... of monitoring? • How is auscultation performed? • How is electronic fetal monitoring performed? • How is external monitoring performed? • ... method of periodically listening to the fetal heartbeat. Electronic fetal monitoring is a procedure in which instruments ...

  16. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

  17. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

  18. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

  19. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

  20. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

  1. Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

    PubMed

    Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

    2015-06-01

    Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart.

    PubMed

    Darby, Jack R T; McMillen, I Caroline; Morrison, Janna L

    2018-06-01

    This study investigates the impact of decreased fetal plasma glucose concentrations on the developing heart in late gestation, by subjecting pregnant ewes to a 50% global nutrient restriction. Late gestation undernutrition (LGUN) decreased fetal plasma glucose concentrations whilst maintaining a normoxemic blood gas status. LGUN increased the mRNA expression of IGF2 and IGF2R. Fetal plasma glucose concentrations, but not fetal blood pressure, were significantly correlated with IGF2 expression and the activation of CAMKII in the fetal right ventricle. LGUN increased interstitial collagen deposition and altered the protein abundance of phospho-PLB and phospho-troponin I, regulators of cardiac contractility and relaxation. This study shows that a decrease in fetal plasma glucose concentrations may play a role in the development of detrimental changes in the right ventricle in early life, highlighting CAMKII as a potential target for the development of intervention strategies. Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The

  3. Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption

    PubMed Central

    Heger, Nicholas E; Hall, Susan J; Sandrof, Moses A; McDonnell, Elizabeth V; Hensley, Janan B; McDowell, Erin N; Martin, Kayla A; Gaido, Kevin W; Johnson, Kamin J

    2012-01-01

    Background: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. Objectives: In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response. Methods: Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points. Results: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression. Conclusions: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis. PMID:22511013

  4. Fluid mechanics of blood flow in human fetal left ventricles based on patient-specific 4D ultrasound scans.

    PubMed

    Lai, Chang Quan; Lim, Guat Ling; Jamil, Muhammad; Mattar, Citra Nurfarah Zaini; Biswas, Arijit; Yap, Choon Hwai

    2016-10-01

    The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic-systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.

  5. Evaluation of prenatal risk factors for prediction of outcome in right heart lesions: CVP score in fetal right heart defects.

    PubMed

    Neves, Ana Luisa; Mathias, Leigh; Wilhm, Marilyn; Leshko, Jennifer; Linask, Kersti K; Henriques-Coelho, Tiago; Areias, José C; Huhta, James C

    2014-09-01

    To determine the prenatal variables predicting the risk of perinatal death in congenital right heart defects. Retrospective analysis of 28 fetuses with right heart defects was performed. Logistic regression analyses were performed to obtain odds ratios (OR) for the relationship between the risk of death and echocardiographic parameters. The parameters that correlated with the outcome were incorporated in an attempt to devise a disease-specific cardiovascular profile score. Fetal echocardiograms (143) from 28 patients were analyzed. The cardiovascular profile score predicted the risk of death. A lower right ventricle (RV) pressure was associated with mortality (OR 0.959; 95% confidence intervals (CI) 0.940-0.978). Higher peak aortic velocity through the aortic valve (OR 0.104; 95% CI 0.020-0.529) was associated with a better outcome. These cardiac function parameters were incorporated in a modified disease-specific CVP Score. Patients with a mean modified cardiovascular profile score of ≤ 6 were over 3.7 times more likely to die than those with scores of 7-10. The original Cardiovascular Profile Score predicted the risk of death in right heart defects. The modified score was not validated as a good prediction tool by this study. Fetal RV pressure estimate and peak aortic velocity can be used as independent prognostic predictors.

  6. Use of Audible and Chart-recorded Ultrasonography to Monitor Fetal Heart Rate and Uterine Blood Flow Parameters in Cattle

    USDA-ARS?s Scientific Manuscript database

    The objective of the present study was to evaluate the use of audible chart-recorded doppler ultrasonography (DUS) to monitor both uterine blood flow and fetal heart rate (FHR) during pregnancy in dairy cattle. Possible applications of DUS include the monitoring of fetal distress when a pregnancy be...

  7. Adrenergic receptors in human fetal liver membranes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Falkay, G.; Kovacs, L.

    1990-01-01

    The adrenergic receptor binding capacities in human fetal and adult livers were measured to investigate the mechanism of the reduced alpha-1 adrenoreceptor response of the liver associated with a reciprocal increase in beta-adrenoreceptor activity in a number of conditions. Alpha-1 and beta-adrenoreceptor density were determined using {sup 3}H-prazosin and {sup 3}H-dihydroalprenolol, respectively, as radioligand. Heterogeneous populations of beta-adrenoreceptors were found in fetal liver contrast to adult. Decreased alpha-1 and increased beta-receptor density were found which may relate to a decreased level in cellular differentiation. These findings may be important for the investigation of perinatal hypoglycemia of newborns after treatment ofmore » premature labor with beta-mimetics. This is the first demonstration of differences in the ratio of alpha-1 and beta-adrenoceptors in human fetal liver.« less

  8. The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs.

    PubMed

    Itskovitz, J; Goetzman, B W; Rudolph, A M

    1982-01-01

    The responses of fetal heart rate and blood pressure to a transient reduction in uterine blood flow were studied in normoxemic and chronically hypoxemic lambs. In normoxemic fetuses, a reduction in uterine blood flow, if prolonged sufficiently, produced reflex bradycardia mediated through chemoreceptors and was associated with a decrease in carotid arterial PO2 to below 20 torr. The bradycardia was associated with a marked decrease in left ventricular output as measured by electromagnetic flowmeter; both were abolished by atropine. In chronically hypoxemic fetuses, a reduction in uterine blood flow produced a delayed deceleration of the heart rate which consisted of three components: reflex bradycardia due to chemoreceptor stimulation; baroreceptor-mediated reflex bradycardia which involved the slow and late recovery of the heart rate; and nonreflex bradycardia which was probably secondary to hypoxic myocardial depression. Quantitative analysis revealed a relationship between the components of delayed deceleration and the status of fetal oxygenation prior to the reduction in uterine blood flow. The lower the carotid arterial PO2, the shorter was the delay in the onset of bradycardia, the greater the decrease in heart rate, and the more prolonged the duration of bradycardia. The conclusion is that the response of fetal heart rate to a transient reduction in uterine blood flow is related to the duration of the reduction and to the status of fetal oxygenation prior to the decrease in uterine blood flow.

  9. Neurodevelopmental Outcome in Children after Fetal Cardiac Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome.

    PubMed

    Laraja, Kristin; Sadhwani, Anjali; Tworetzky, Wayne; Marshall, Audrey C; Gauvreau, Kimberlee; Freud, Lindsay; Hass, Cara; Dunbar-Masterson, Carolyn; Ware, Janice; Lafranchi, Terra; Wilkins-Haug, Louise; Newburger, Jane W

    2017-05-01

    To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment. Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory. Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms (P < .001) and similar to published reports in patients with hypoplastic left heart syndrome without fetal intervention; scores in the single ventricular versus biventricular group were 97 ± 19 vs 89 ± 14, respectively (P = .10). On multivariable analysis, independent predictors of a lower General Adaptive Composite score were total hospital duration of stay in the first year of life (P = .001) and, when forced into the model, biventricular status (P = .02). For all other neurodevelopmental questionnaires (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar. Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy

  10. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  11. Intact Imaging of Human Heart Structure Using X-ray Phase-Contrast Tomography.

    PubMed

    Kaneko, Yukihiro; Shinohara, Gen; Hoshino, Masato; Morishita, Hiroyuki; Morita, Kiyozo; Oshima, Yoshihiro; Takahashi, Masashi; Yagi, Naoto; Okita, Yutaka; Tsukube, Takuro

    2017-02-01

    Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.

  12. Assessment of umbilical artery flow and fetal heart rate to predict delivery time in bitches.

    PubMed

    Giannico, Amália Turner; Garcia, Daniela Aparecida Ayres; Gil, Elaine Mayumi Ueno; Sousa, Marlos Gonçalves; Froes, Tilde Rodrigues

    2016-10-15

    The aim of this study was to quantitatively investigate the oscillation of the fetal heart rate (HR) in advance of normal delivery and whether this index could be used to indicate impending delivery. In addition, fetal HR oscillation and umbilical artery resistive index (RI) were correlated to determine if the combination of these parameters provided a more accurate prediction of the time of delivery. Sonographic evaluation was performed in 11 pregnant bitches to evaluate the fetal HR and umbilical artery RI at the following antepartum times: 120 to 96 hours, 72 to 48 hours, 24 to 12 hours, and 12 to 1 hours. Statistical analysis indicated a correlation between the oscillation of fetal HR and the umbilical artery RI. As delivery approached a considerable reduction in the umbilical artery RI was documented and greater oscillations between maximum and minimum HRs occurred. We conclude that the quantitative analysis of fetal HR oscillations may be used to predict the time of delivery in bitches. The combination of fetal HR and umbilical artery RI together may provide more accurate predictions of time of delivery. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Computerized analysis of fetal heart rate variability signal during the stages of labor.

    PubMed

    Annunziata, Maria Laura; Tagliaferri, Salvatore; Esposito, Francesca Giovanna; Giuliano, Natascia; Mereghini, Flavia; Di Lieto, Andrea; Campanile, Marta

    2016-03-01

    To analyze computerized cardiotocographic (cCTG) parameters (baseline fetal heart rate, baseline FHR; short term variability, STV; approximate entropy, ApEn; low frequency, LF; movement frequency, MF; high frequency, HF) in physiological pregnancy in order to correlate them with the stages of labor. This could provide more information for understanding the mechanisms of nervous system control of FHR during labor progression. A total of 534 pregnant women were monitored on cCTG from the 37th week before the onset of spontaneous labor and during the first and the second stage of labor. Statistical analysis was performed using Kruskal-Wallis test and Wilcoxon rank-sum test with the Bonferroni adjusted α (< 0.05). Statistically significant differences were seen between baseline FHR, MF and HF (P < 0.001), in which the first two were reduced and the third was increased when compared between pre-labor, and the first and second stages of labor. Differences between some of the stages were found for ApEn, LF and for LF/(HF + MF), where the first and the third were reduced and the second was increased. cCTG modifications during labor may reflect the physiologic increased activation of the autonomous nervous system. Using computerized fetal heart rate analysis during labor it may be possible to obtain more information from the fetal cardiac signal, in comparison with the traditional tracing. © 2016 Japan Society of Obstetrics and Gynecology.

  14. A PKM2 signature in the failing heart

    PubMed Central

    Rees, Meredith L.; Subramaniam, Janani; Li, Yuanteng; Hamilton, Dale J.; Frazier, O. Howard; Taegtmeyer, Heinrich

    2015-01-01

    A salient feature of the failing heart is metabolic remodeling towards predominant glucose metabolism and activation of the fetal gene program. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor used for the treatment of highly vascularized tumors. In diabetic patients, sunitinib significantly decreases blood glucose. However, a considerable proportion of sunitinib-treated patients develop cardiac dysfunction or failure. We asked whether sunitinib treatment results in shift towards glycolysis in the heart. Glucose uptake by the heart was increased fivefold in mice treated with sunitinib. Transcript analysis by qPCR revealed an induction of genes associated with glycolysis and reactivation of the fetal gene program. Additionally, we observed a shift in the enzyme pyruvate kinase from the adult M1 (PKM1) isoform to the fetal M2 (PKM2) isoform, a hallmark of the Warburg Effect. This novel observation led us to examine whether a similar shift occurs in human heart failure. Examination of tissue from patients with heart failure similarly displayed an induction of PKM2. Moreover, this phenomenon was partially reversed following mechanical unloading. We propose that pyruvate kinase isoform switching represents a novel feature of the fetal gene program in the failing heart. PMID:25735978

  15. Clinical application of pulse transit time and correlation with intrapartum fetal heart rate monitoring: a preliminary study of 18 full-term infants.

    PubMed

    Kawagoe, Yasuyuki; Sameshima, Hiroshi; Ikenoue, Tsuyomu

    2008-07-01

    The authors show that pulse transit time and blood pressure are reciprocal in fetal goat models. They applied this technique in clinical settings to correlate changes in pulse transit time with fetal heart rate monitoring patterns and acid-base status. In 18 uncomplicated pregnancies, pulse transit time was obtained from electrocardiograms to pulse oximeter waveform and averaged during each baseline period, defined by the interpretation of fetal heart rate monitoring. According to a > 10% change from the control value, chronological changes were categorized into shortened, unchanged, and prolonged. Pulse transit time was available in 82% +/- 11% of the recordings. In 15 fetuses, 2 (13%) showed prolonged, 7 (47%) showed shortened, and 6 (40%) showed unchanged conditions. Comparisons of the shortened and unchanged categories revealed that severe variable deceleration was significantly increased, and half or more fetuses showed hypoxemia in the shortened category. Shortening of pulse transit time, theoretically indicating a hypertensive condition, was more frequently associated with severe variable decelerations, suggesting that the pulse transit time may supplement the interpretation of fetal heart rate monitoring.

  16. Evaluating Spatiotemporal Image Correlation Technology as a Tool for Training Nonexpert Sonographers to Perform Examinations of the Fetal Heart.

    PubMed

    Avnet, Hagai; Mazaaki, Eyal; Shen, Ori; Cohen, Sarah; Yagel, Simcha

    2016-01-01

    We aimed to evaluate the use of spatiotemporal image correlation (STIC) as a tool for training nonexpert examiners to perform screening examinations of the fetal heart by acquiring and examining STIC volumes according to a standardized questionnaire based on the 5 transverse planes of the fetal heart. We conducted a prospective study at 2 tertiary care centers. Two sonographers without formal training in fetal echocardiography received theoretical instruction on the 5 fetal echocardiographic transverse planes, as well as STIC technology. Only women with conditions allowing 4-dimensional STIC volume acquisitions (grayscale and Doppler) were included in the study. Acquired volumes were evaluated offline according to a standardized protocol that required the trainee to mark 30 specified structures on 5 required axial planes. Volumes were then reviewed by an expert examiner for quality of acquisition and correct identification of specified structures. Ninety-six of 112 pregnant women examined entered the study. Patients had singleton pregnancies between 20 and 32 weeks' gestation. After an initial learning curve of 20 examinations, trainees succeeded in identifying 97% to 98% of structures, with a highly significant degree of agreement with the expert's analysis (P < .001). A median of 2 STIC volumes for each examination was necessary for maximal structure identification. Acquisition quality scores were high (8.6-8.7 of a maximal score of 10) and were found to correlate with identification rates (P = .017). After an initial learning curve and under expert guidance, STIC is an excellent tool for trainees to master extended screening examinations of the fetal heart.

  17. Fetal Heart Rate Monitoring During Surgical Correction of Spontaneous Pneumothorax During Pregnancy: Lessons in In Utero Resuscitation.

    PubMed

    Wilson, Bailey; Burt, Bryan; Baker, Byron; Clark, Steven L; Belfort, Michael; Gandhi, Manisha

    2016-01-01

    Spontaneous pneumothorax during pregnancy has potentially serious implications for the mother and fetus. When surgical correction is required, complex maternal physiologic alterations may significantly affect fetal well-being. A woman underwent thoracoscopic lung resection and pleurodesis at 29 weeks of gestation. At various points during the procedure, maternal hemodynamic and respiratory consequences of anesthetic and surgical management resulted in severe fetal heart rate (FHR) decelerations and bradycardia. In each instance, physiologic manipulations based on an understanding of the likely cause of fetal hypoxia allowed correction of the FHR abnormalities without delivery. Nonsurgical perinatal intervention based on FHR monitoring and analysis of the likely pathophysiologic abnormalities underlying fetal decelerations may allow the gravid woman to undergo complex procedures and continue the pregnancy.

  18. Fetal Heart Rate and Variability: Stability and Prediction to Developmental Outcomes in Early Childhood

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; Bornstein, Marc H.; Hahn, Chun-Shin; Costigan, Kathleen; Achy-Brou, Aristide

    2007-01-01

    Stability in cardiac indicators before birth and their utility in predicting variation in postnatal development were examined. Fetal heart rate and variability were measured longitudinally from 20 through 38 weeks gestation (n = 137) and again at age 2 (n = 79). Significant within-individual stability during the prenatal period and into childhood…

  19. Maternal and fetal outcomes in pregnant women with heart failure.

    PubMed

    Ng, Angie T; Duan, Lewei; Win, Theresa; Spencer, Hillard T; Lee, Ming-Sum

    2018-05-25

    The goal of this study is to report the prevalence, aetiology and clinical outcome of pregnant women with heart failure. This is a retrospective community-based cohort study that included pregnant women in the Kaiser Permanente Health System between 2003 and 2014. Women with heart failure were identified using International Classification of Disease, Ninth Revision codes. Medical records were manually reviewed to confirm diagnosis and adjudicate outcomes. In a cohort of 385 935 pregnancies, 488 (0.13%) had a diagnosis of heart failure, corresponding to 126 cases per 100 000 pregnancies. Peripartum cardiomyopathy was the most common cause of heart failure, accounting for 333 (68.2%) cases. Preterm birth and caesarean delivery were more common in patients with heart failure. Neonatal death rate was higher in the heart failure group (1.0% vs 0.4%, p=0.03). Infants delivered to women with heart failure had lower birth weights (3112.0±774.0 g vs 3331.9±575.5 g, p<0.001) and lower Apgar score at 1 min (7.9±1.5 vs 8.3±1.1, p<0.001). Median follow-up was 6.2 years (IQR 3.2-9.2). During follow-up, 7 (1.4%) in the heart failure group and 423 (0.11%) in the control group died. Heart failure was associated with a 7.7-fold increase risk of death (adjusted HR 7.7, 95% CI 3.6 to 16.4, p<0.001). Heart failure during pregnancy is associated with unfavourable fetal outcomes including prematurity and low birth weight. While the overall mortality rate was low, pregnant women with heart failure carried an excess risk of death compared with controls. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Reducing sojourn points from recurrence plots to improve transition detection: Application to fetal heart rate transitions.

    PubMed

    Zaylaa, Amira; Charara, Jamal; Girault, Jean-Marc

    2015-08-01

    The analysis of biomedical signals demonstrating complexity through recurrence plots is challenging. Quantification of recurrences is often biased by sojourn points that hide dynamic transitions. To overcome this problem, time series have previously been embedded at high dimensions. However, no one has quantified the elimination of sojourn points and rate of detection, nor the enhancement of transition detection has been investigated. This paper reports our on-going efforts to improve the detection of dynamic transitions from logistic maps and fetal hearts by reducing sojourn points. Three signal-based recurrence plots were developed, i.e. embedded with specific settings, derivative-based and m-time pattern. Determinism, cross-determinism and percentage of reduced sojourn points were computed to detect transitions. For logistic maps, an increase of 50% and 34.3% in sensitivity of detection over alternatives was achieved by m-time pattern and embedded recurrence plots with specific settings, respectively, and with a 100% specificity. For fetal heart rates, embedded recurrence plots with specific settings provided the best performance, followed by derivative-based recurrence plot, then unembedded recurrence plot using the determinism parameter. The relative errors between healthy and distressed fetuses were 153%, 95% and 91%. More than 50% of sojourn points were eliminated, allowing better detection of heart transitions triggered by gaseous exchange factors. This could be significant in improving the diagnosis of fetal state. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Association of Fetal Heart Rate Baseline Change and Neonatal Outcomes.

    PubMed

    Yang, Michael; Stout, Molly J; López, Julia D; Colvin, Ryan; Macones, George A; Cahill, Alison G

    2017-07-01

    Objective  The objective of this study was to describe the incidence of baseline change within normal range during labor and its prediction of neonatal outcomes. Materials and Methods  This was a prospective cohort of singleton, nonanomalous, term neonates with continuous electronic fetal monitoring and normal baseline fetal heart rate throughout the last 2 hours of labor. We determined baseline in 10-minute segments using Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria. We evaluated baseline changes of ≥ 20 and ≥ 30 bpm for association with acidemia (umbilical cord arterial pH ≤ 7.10) and neonatal intensive care unit (NICU) admission. Finally, we performed a sensitivity analysis of normal neonates, excluding those with acidemia, NICU admission, or 5-minute Apgar < 4. Results  Among all neonates ( n  = 3,021), 1,267 (41.9%) had change ≥ 20 bpm; 272 (9.0%) had ≥ 30 bpm. Among normal neonates ( n  = 2,939), 1,221 (41.5%) had change ≥20 bpm. Acidemia was not associated with baseline change of any direction or magnitude. NICU admission was associated with decrease ≥ 20 bpm (adjusted odds ratio [aOR]: 2.93; 95% confidence interval [CI]: 1.19 - 7.21) or any direction ≥ 20 bpm (aOR: 4.06; 95% CI: 1.46-11.29). For decrease ≥ 20 bpm, sensitivity and specificity were 40.0 and 81.7%; for any direction ≥ 20 bpm, 75.0 and 58.3%. Conclusion  Changes of normal baseline are common in term labor and poorly predict morbidity, regardless of direction or magnitude. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Engineering human ventricular heart muscles based on a highly efficient system for purification of human pluripotent stem cell-derived ventricular cardiomyocytes.

    PubMed

    Li, Bin; Yang, Hui; Wang, Xiaochen; Zhan, Yongkun; Sheng, Wei; Cai, Huanhuan; Xin, Haoyang; Liang, Qianqian; Zhou, Ping; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yang, Pengyuan; Zhang, Jianyi; Shou, Weinian; Huang, Guoying; Liang, Ping; Sun, Ning

    2017-09-29

    Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish. The purification system used TALEN-mediated genomic editing techniques to insert the neomycin or EGFP selection marker directly after the myosin light chain 2 (MYL2) locus in human pluripotent stem cells. Purified early ventricular cardiomyocytes were estimated by immunofluorescence, fluorescence-activated cell sorting, quantitative PCR, microelectrode array, and patch clamp. In subsequent experiments, the mixture of mature MYL2-positive ventricular cardiomyocytes and mesenchymal cells were cocultured with decellularized natural heart matrix. Histological and electrophysiology analyses of the formed tissues were performed 2 weeks later. Human ventricular cardiomyocytes were efficiently isolated based on the purification system using G418 or flow cytometry selection. When combined with the decellularized natural heart matrix as the scaffold, functional human ventricular heart muscles were prepared in a dish. These engineered human ventricular muscles can be great tools for regenerative therapy of human ventricular damage as well as drug screening and ventricular-specific disease modeling in the future.

  3. Toward the improvement in fetal monitoring during labor with the inclusion of maternal heart rate analysis.

    PubMed

    Gonçalves, Hernâni; Pinto, Paula; Silva, Manuela; Ayres-de-Campos, Diogo; Bernardes, João

    2016-04-01

    Fetal heart rate (FHR) monitoring is used routinely in labor, but conventional methods have a limited capacity to detect fetal hypoxia/acidosis. An exploratory study was performed on the simultaneous assessment of maternal heart rate (MHR) and FHR variability, to evaluate their evolution during labor and their capacity to detect newborn acidemia. MHR and FHR were simultaneously recorded in 51 singleton term pregnancies during the last two hours of labor and compared with newborn umbilical artery blood (UAB) pH. Linear/nonlinear indices were computed separately for MHR and FHR. Interaction between MHR and FHR was quantified through the same indices on FHR-MHR and through their correlation and cross-entropy. Univariate and bivariate statistical analysis included nonparametric confidence intervals and statistical tests, receiver operating characteristic curves and linear discriminant analysis. Progression of labor was associated with a significant increase in most MHR and FHR linear indices, whereas entropy indices decreased. FHR alone and in combination with MHR as FHR-MHR evidenced the highest auROC values for prediction of fetal acidemia, with 0.76 and 0.88 for the UAB pH thresholds 7.20 and 7.15, respectively. The inclusion of MHR on bivariate analysis achieved sensitivity and specificity values of nearly 100 and 89.1%, respectively. These results suggest that simultaneous analysis of MHR and FHR may improve the identification of fetal acidemia compared with FHR alone, namely during the last hour of labor.

  4. Fetal Antecedents of Infant Temperament.

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; And Others

    1996-01-01

    Examined fetal heart rate and movement in 31 healthy fetuses from 20 weeks through birth and at age 6 months. Found that more active fetuses were more difficult, unpredictable, unadaptable, and active as infants that were less active fetuses, and that higher fetal heart rate was associated with lower emotional tone, activity level, and…

  5. Uterine artery blood flow, fetal hypoxia and fetal growth

    PubMed Central

    Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  6. The short-term effect of smoking on fetal ECG.

    PubMed

    Péterfi, István; Kellényi, Lóránd; Péterfi, Lehel; Szilágyi, András

    2017-10-26

    The number of women who smoke during pregnancy is significant even today. The harmful effects of smoking during pregnancy are well known but there are no data on the effects of smoking on fetal electrocardiography (ECG). The lack of data is in connection with the difficulties of recording fetal ECG through the maternal abdomen. Third trimester pregnant women who were not able to give up the harmful passion of smoking despite repeated attempts of persuasion were recruited in the study on voluntary basis. The fetal ECG was recorded non-invasively through the maternal abdomen before, during and after smoking, then the data were processed offline. The electrophysiological measurements were performed by a self developed ECG device, which allowed the examination of the morphological differences in "true-to-form" fetal ECG in addition to studying the variability of fetal heart rate. The study involved nine pregnant women. The observed changes are presented through case studies of those pregnant women who showed the most significant anomalies. Compared with the resting state fetal heart rate was increased during smoking. The short-term variability of fetal heart rate was narrowed, while the mother's heart rate did not change significantly - which was an indication of direct fetal stress. No explicit ischemic signs were detected in fetal ECG during smoking, however, in the increasing period of the fetal heart rate, the T wave morphology changed slightly, then it returned to normal. Demonstrable by the electrophysiological methods, smoking has a direct effect on fetal cardiac function. The fetal heart rate variability shows a pattern during smoking which is a typical sign of stress conditions among adults. The results may have educational consequences as well. Understanding those, hopefully will help pregnant women give up this harmful addiction.

  7. Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth

    PubMed Central

    Song, Limei; Mishra, Virendra; Ouyang, Minhui; Peng, Qinmu; Slinger, Michelle; Liu, Shuwei; Huang, Hao

    2017-01-01

    Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural

  8. Retinoic Acid Signalling and the Control of Meiotic Entry in the Human Fetal Gonad

    PubMed Central

    Kinnell, Hazel L.; Anderson, Richard A.; Saunders, Philippa T. K.

    2011-01-01

    The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA). Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8–9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may be important in

  9. Fetal Heart Rate Reactivity Differs by Women's Psychiatric Status: An Early Marker for Developmental Risk?

    ERIC Educational Resources Information Center

    Monk, Catherine; Sloan, Richard P.; Myers, Michael M.; Ellman, Lauren; Werner, Elizabeth; Jeon, Jiyeon; Tager, Felice; Fifer, William P.

    2004-01-01

    Objective: To determine whether there are differences in fetal heart rate (FHR) reactivity associated with women's psychiatric status. Method: In 57 women in their 36th to 38th week of pregnancy (mean age 27 [+ or -] 6 years), electrocardiogram, blood pressure (BP), respiration (RSP), and FHR were measured during baseline and a psychological…

  10. Telemedicine for antenatal surveillance of high-risk pregnancies with ambulatory and home fetal heart rate monitoring--an update.

    PubMed

    Hod, Moshe; Kerner, Ram

    2003-01-01

    Antepartum fetal surveillance is routinely used to assess the risk of fetal death in high-risk pregnancies. Traditionally, testing is performed in the hospital or outpatient clinic by trained medical staff. New equipment is now available that is easy to operate and can be used for self-monitoring of the fetal heart rate (FHR) in the home setting. The tracings are transmitted by modem to a referral center for immediate interpretation by a health provider. The aim of this review was to assess the current data on the application of this new technology with regard to feasibility, access to care, maternal and neonatal outcome, patient and physician satisfaction, and cost-effectiveness.

  11. Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases: An NHLBI Resource for the Gene Therapy Community

    PubMed Central

    Skarlatos, Sonia I.

    2012-01-01

    Abstract The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; “proof-of-principle”; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field. PMID:22974119

  12. Influence of Gestational Overfeeding on Myocardial Pro-inflammatory Mediators in Fetal Sheep Heart

    PubMed Central

    Kandadi, Machender R.; Hua, Yinan; Zhu, Meijun; Turdi, Subat; Nathanielsz, Peter W.; Ford, Stephen P.; Nair, Sreejayan; Ren, Jun

    2013-01-01

    Maternal overnutrition is associated with predisposition of offspring to cardiovascular disease in later life. Since maternal overnutrition may promote fetal and placental inflammatory responses, we hypothesized that maternal overnutrition/obesity increases expression of fetal cardiac proinflammatory mediators and alter cardiac morphometry. Multiparous ewes were fed either 150% of National Research Council (NRC) nutrient recommendations (overfed) or 100% of NRC requirement (control) from 60 days prior to mating to gestation day 75 (D75), when ewes were euthanized. An additional cohort of overfed and control ewes were necropsied on D135. Cardiac morphometry, histology, mRNA and protein expression of TLR4, iNOS, IL-1a, IL-1b, IL-6, IL-18, CD-14, CD-68, M-CSF and protein levels of phosphorylated I-κB and NF-κB were examined. Immunohistochemistry was performed to assess neutrophil and monocyte infiltration. Crown rump length, left and right ventricular free wall weights as well as left and right ventricular wall thickness were significantly increased in D75 fetuses of overfed mothers. Hematoxylin and eosin staining revealed irregular myofiber orientation and increased interstitial space in fetal ventricular tissues born to overfed mothers. Oil red O staining exhibited marked lipid droplet accumulation in the overfed fetuses. Overfeeding significantly enhanced TLR-4, IL-1a, IL-1b IL-6 expression, promoted phosphorylation of IκB, decreased cytoplasmic NF-κB levels and increased neutrophil and monocyte infiltration. Collectively, these data suggest that maternal overfeeding prior to and throughout gestation leads to inflammation in the fetal heart and alters fetal cardiac morphometry. PMID:24075902

  13. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    PubMed

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  14. Diagnosis and Treatment of Fetal Arrhythmia

    PubMed Central

    Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

    2014-01-01

    Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

  15. [Fetal echocardiography efficiency. Clinical experience].

    PubMed

    San Luis Miranda, Raúl; Arias Monroy, Laura Guadalupe; Gutiérrez González, Gladis Alicia; León Avila, José Luis; Cruz Rodríguez, Armando; Osornio Correa, Porfirio Rafael

    2008-12-01

    Congenital heart disease diagnostic has a high diagnostic precision with fetal echocardiography. This study has been reported in populations with high risk and with a sensibility of 86 to 99% and specificity of 91 to 100%. To know sensibility and specificity of fetal echocardiography in high-risk pregnancies, and to describe types and frequency of congenital heart disease in utero. 229 files of pregnant women with high-risk factors, more than 15 weeks of gestation, and at birth cardiovascular exam were analyzed. This analysis was made by means of simple frequencies, sensibility, specificity, positive and negative predictive value, and truth index calculation. We found 62 (27%) cases with fetal heart disease. Mean of maternal age was 27 +/- 5.5 years, and of gestational age 31 +/- 5 weeks. Risk factors that require study were: four-chamber abnormality in routine ultrasound, dysmorphy, fetal bradicardia, and poll and oligohydramnios. There were 55 (88.7%) high-risk heart diseases, and most frequent were Ebstein's anomaly, unique ventricle, hypoplastic left ventricle syndrome, and tumors. Sensibility was 98.41%, specificity was 97.59%, positive prognostic value was 97.59%, and negative prognostic value was 99.39%. Fetal echocardiography has a high diagnosis certainty in our hospital unit, thus, it has to be a normal prenatal exam in pregnant women with high-risk factors.

  16. Computerized fetal heart rate monitoring after vibroacoustic stimulation in the anencephalic fetus.

    PubMed

    Park, Yong-Jin; Park, Seon-Hye; Kim, Young-Jae; Hoh, Jeong-Kyu; Park, Young-Sun; Park, Moon-Il

    2010-09-01

    To quantify changes in fetal heart rate (FHR) parameters after vibroacoustic stimulation (VAS) and to evaluate the usefulness of VAS testing (VAST) in anencephalic fetuses. Our findings may also help to clarify the route(s) of vibration and sound transmission during VAST. We obtained the antepartum FHR tracings of 16 anencephalic fetuses, including both the nonstress test (NST) and VAST. Using a computerized monitoring system, HYFM, we determined all FHR parameters from data collected for 10 min before and 10 min after VAS, at successive gestational stages. We observed three false reactive responses at term. The false reactive rate for VAST (3/16) was higher than that for NST (1/16). No FHR parameters increased significantly after VAS except for the number of fetal movements (FM), which increased significantly in all gestational groups (25th-32nd and 33rd-40th weeks). These findings call attention to an increased probability of a false reactive response in VAST analysis, when the fetus is affected by a CNS disorder. Increased numbers of FM after VAS suggest that the vibratory pathway is more likely to elicit fetal response than the auditory pathway in this setting, and that the vibratory stimulation travels by subcortical rather than by cortical pathways. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Ethics, public policy, and human fetal tissue transplantation research.

    PubMed

    Childress, James F

    1991-06-01

    This article focuses on the deliberations of the National Institutes of Health Human Fetal Tissue Transplantation Research Panel in 1988. It explores various arguments for and against the use of fetal tissue for transplantation research, following elective abortion, and for and against the use of federal funds for such research. After examining the relevance of various positions on the moral status of the fetus and the morality of abortion, the article critically examines charges that such research, especially with federal funds, would involve complicity in the moral evil of abortion, would legitimate abortion practices, and would provide incentives for abortions. Finally, it considers whether the donation model is appropriate for the transfer of human fetal tissue and whether the woman who chooses to have an abortion is the apppropriate donor of the tissue.

  18. Accelerated acidosis in response to variable fetal heart rate decelerations in chronically hypoxic ovine fetuses.

    PubMed

    Amaya, Kevin E; Matushewski, Brad; Durosier, L Daniel; Frasch, Martin G; Richardson, Bryan S; Ross, Michael G

    2016-02-01

    Due to limitations of technology, clinicians are typically unable to determine if human fetuses are normoxic or moderately, chronically hypoxic. Risk factors for chronic hypoxia include fetal growth restriction, which is associated with an increased incidence of oligohydramnios and thus a risk for umbilical cord occlusion (UCO) and variable fetal heart rate (FHR) decelerations. At delivery, fetal growth restriction infants (<3rd percentile) have nearly twice the incidence of low Apgar scores and umbilical pH <7.0. Despite the risks of oligohydramnios and intermittent UCO, there is little understanding of the acid/base responses rates of chronically hypoxic fetuses to variable FHR decelerations as might occur during human labor. We sought to compare the increase in base deficit (BD) among chronically hypoxic as compared to normoxic ovine fetuses in response to simulated mild, moderate, and severe variable FHR decelerations. Near-term ovine fetuses were chronically prepared with brachial artery catheters and an inflatable umbilical cuff occluder. Following a recovery period, normoxic (n = 9) and spontaneously hypoxic (n = 5) fetuses were identified (arterial O2 saturation ≤55%). Both animal groups underwent graded, 1-minute occlusions every 2.5 minutes with 1 hour of mild (∼30 beats/min [bpm] decrease from baseline), 1 hour of moderate (∼60 bpm decrease from baseline), and up to 2 hours of severe (∼90 bpm decrease from baseline) variable FHR decelerations until fetal arterial pH reached 7.00, when occlusions were stopped. Repetitive UCO resulted in development of acidosis (pH <7.0) in both groups. Hypoxic and normoxic fetuses demonstrated similar BD increases in response to both mild (0.39, interquartile range [IQR] 0.28-0.45 vs 0.26, IQR 0.01-0.30 mEq/L/10 min, P = .25) and severe (1.97, IQR 1.50-2.43 vs 1.51, IQR 0.97-2.45 mEq/L/10 min, P = .63) variable decelerations. However, moderate variable decelerations increased BD in hypoxic fetuses at 2.5 times the

  19. Comparison of fetal and maternal heart rate measures using electrocardiographic and cardiotocographic methods.

    PubMed

    Kisilevsky, Barbara S; Brown, C Ann

    2016-02-01

    To determine the reliability at term of: (1) two methods of measuring fetal heart rate (HR), electrocardiographic (ECG, the 'gold standard') and cardiotocographic (CTG) and (2) two ECG methods of measuring maternal HR variability over relatively brief periods of time (s-min). During 20 min of rest (N=39) and during 2 min of auditory stimulation (mother's recorded voice, n=19), fetal HR data were collected using an ECG (Monica AN24) and a Hewlett-Packard Model 1351A CTG. Simultaneously, maternal HR data (n=37) were collected using the same ECG device (Monica AN24) and a second stand-alone cardiac monitor (Spacelab 514T cardiac monitor with a QRS detector). During 20 min of maternal rest, correlations of individual fetal CTG with ECG measures of HR at each second were moderate to high (r=.57-.97) for 77% of fetuses. Correlations of HR averaged over fetuses and over each of the 20 min were high (r=.93-.97); fetal HR averaged over 20 min varied between devices from 0.0 to 0.8 bpm. During 2 min of maternal voice presentation, correlations of fetal HR over each second were moderate to high (r=.54-.99) for 95% of fetuses and high (all rs=.99) when averaged across fetuses in 30s or 2 min epochs. Average fetal HR between devices over the 2 min voice varied from 0.0 to 0.6 bpm. Correlations and/or % agreement between the two ECG methods of measuring maternal HR were high. Average maternal HR over 10 min showed 81% of pairs with a difference of ≤ 1 bpm; correlations for HR variability measures varied from r=.89 to .97. Good reliability was demonstrated between individual spontaneous and auditory induced fetal CTG and ECG with high correlations when HR data were averaged over fetuses or in 30-120 s epochs. High reliability of maternal HR measures was obtained using two ECG devices. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A portable fetal heart monitor and its adaption to the detection of certain prenatal abnormalities

    NASA Technical Reports Server (NTRS)

    Zahorian, Stephen A.

    1994-01-01

    There were three primary objectives for this task: (1) The investigation of the feasibility of making the fetal heart rate monitor portable, using a laptop computer; (2) Improvements in the signal processing for the monitor; and (3) Implementation of a real-time hardware software system. These tasks have been completed as discussed in the following section.

  1. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development

    PubMed Central

    Camp, J. Gray; Badsha, Farhath; Florio, Marta; Kanton, Sabina; Gerber, Tobias; Wilsch-Bräuninger, Michaela; Lewitus, Eric; Sykes, Alex; Hevers, Wulf; Lancaster, Madeline; Knoblich, Juergen A.; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B.; Treutlein, Barbara

    2015-01-01

    Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. PMID:26644564

  2. mAb C19 targets a novel surface marker for the isolation of human cardiac progenitor cells from human heart tissue and differentiated hESCs.

    PubMed

    Leung, Hau Wan; Moerkamp, Asja T; Padmanabhan, Jayanthi; Ng, Sze-Wai; Goumans, Marie-José; Choo, Andre

    2015-05-01

    Cardiac progenitor cells (CPCs) have been isolated from adult and developing hearts using an anti-mouse Sca-1 antibody. However, the absence of a human Sca-1 homologue has hampered the clinical application of the CPCs. Therefore, we generated novel monoclonal antibodies (mAbs) specifically raised against surface markers expressed by resident human CPCs. Here, we explored the suitability of one of these mAbs, mAb C19, for the identification, isolation and characterization of CPCs from fetal heart tissue and differentiating cultures of human embryonic stem cells (hESCs). Using whole-cell immunization, mAbs were raised against Sca-1+ CPCs and screened for reactivity to various CPC lines by flow cytometry. mAb C19 was found to be specific for Sca-1+ CPCs, with high cell surface binding capabilities. mAb C19 stained small stem-like cells in cardiac tissue sections. Moreover, during differentiation of hESCs towards cardiomyocytes, a transient population of cells with mAb C19 reactivity was identified and isolated using magnetic-activated cell sorting. Their cell fate was tracked and found to improve cardiomyocyte purity from hESC-derived cultures. mAb C19+ CPCs, from both hESC differentiation and fetal heart tissues, were maintained and expanded in culture, while retaining their CPC-like characteristics and their ability to further differentiate into cardiomyocytes by stimulation with TGFβ1. Finally, gene expression profiling of these mAb C19+ CPCs suggested a highly angiogenic nature, which was further validated by cell-based angiogenesis assays. mAb C19 is a new surface marker for the isolation of multipotent CPCs from both human heart tissues and differentiating hESCs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Filtering and left ventricle segmentation of the fetal heart in ultrasound images

    NASA Astrophysics Data System (ADS)

    Vargas-Quintero, Lorena; Escalante-Ramírez, Boris

    2013-11-01

    In this paper, we propose to use filtering methods and a segmentation algorithm for the analysis of fetal heart in ultrasound images. Since noise speckle makes difficult the analysis of ultrasound images, the filtering process becomes a useful task in these types of applications. The filtering techniques consider in this work assume that the speckle noise is a random variable with a Rayleigh distribution. We use two multiresolution methods: one based on wavelet decomposition and the another based on the Hermite transform. The filtering process is used as way to strengthen the performance of the segmentation tasks. For the wavelet-based approach, a Bayesian estimator at subband level for pixel classification is employed. The Hermite method computes a mask to find those pixels that are corrupted by speckle. On the other hand, we picked out a method based on a deformable model or "snake" to evaluate the influence of the filtering techniques in the segmentation task of left ventricle in fetal echocardiographic images.

  4. Fetal Neurobehavioral Development.

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; And Others

    1996-01-01

    Investigated the ontogeny of fetal autonomic, motoric, state, and interactive functioning in 31 healthy fetuses from 20 weeks through term. Found that male fetuses were more active than female fetuses, and that greater maternal stress appraisal was associated with reduced fetal heart rate variability. Found that an apparent period of…

  5. Near-term fetal response to maternal spoken voice

    PubMed Central

    Voegtline, Kristin M.; Costigan, Kathleen A.; Pater, Heather A.; DiPietro, Janet A.

    2013-01-01

    Knowledge about prenatal learning has been largely predicated on the observation that newborns appear to recognize the maternal voice. Few studies have examined the process underlying this phenomenon; that is, whether and how the fetus responds to maternal voice in situ. Fetal heart rate and motor activity were recorded at 36 weeks gestation (n = 69) while pregnant women read aloud from a neutral passage. Compared to a baseline period, fetuses responded with a decrease in motor activity in the 10-seconds following onset of maternal speech and a trend level decelerative heart rate response, consistent with an orienting response. Subsequent analyses revealed that the fetal response was modified by both maternal and fetal factors. Fetuses of women who were previously awake and talking (n = 40) showed an orienting response to onset of maternal reading aloud, while fetuses of mothers who had previously been resting and silent (n = 29) responded with elevated heart rate and increased movement. The magnitude of the fetal response was further dependent on baseline fetal heart rate variability such that largest response was demonstrated by fetuses with low variability of mothers who were previously resting and silent. Results indicate that fetal responsivity is affected by both maternal and fetal state and have implications for understanding fetal learning of the maternal voice under naturalistic conditions. PMID:23748167

  6. Intelligent Structured Intermittent Auscultation (ISIA): evaluation of a decision-making framework for fetal heart monitoring of low-risk women

    PubMed Central

    2014-01-01

    Background Research-informed fetal monitoring guidelines recommend intermittent auscultation (IA) for fetal heart monitoring for low-risk women. However, the use of cardiotocography (CTG) continues to dominate many institutional maternity settings. Methods A mixed methods intervention study with before and after measurement was undertaken in one secondary level health service to facilitate the implementation of an initiative to encourage the use of IA. The intervention initiative was a decision-making framework called Intelligent Structured Intermittent Auscultation (ISIA) introduced through an education session. Results Following the intervention, medical records review revealed an increase in the use of IA during labour represented by a relative change of 12%, with improved documentation of clinical findings from assessments, and a significant reduction in the risk of receiving an admission CTG (RR 0.75, 95% CI, 0.60 – 0.95, p = 0.016). Conclusion The ISIA informed decision-making framework transformed the practice of IA and provided a mechanism for knowledge translation that enabled midwives to implement evidence-based fetal heart monitoring for low risk women. PMID:24884597

  7. Fetal heart rate monitoring category 3 during the 2nd stage of labor is an independent predictor of fetal acidosis.

    PubMed

    Silberstein, Tali; Sheiner, Eyal; Salem, Shimrit Yaniv; Hamou, Batel; Aricha, Barak; Baumfeld, Yael; Yohay, Zehava; Elharar, Debora; Idan, Inbal; Yohay, David

    2017-02-01

    To determine whether fetal heart rate (FHR) monitoring categories during the 1st and 2nd stage of labor can predict arterial cord pH <7.2. A case control study was conducted including 653 consecutive term deliveries (37 weeks gestation and above) that were divided according to fetal pH ≤ 7.2 (n = 315) and fetal pH > 7.2 (n = 338). Deliveries occurred during the year 2013 in tertiary medical center, where arterial cord pH is routinely taken after birth. Intrapartum FHR monitoring categorization was defined according to the ACOG committee guidelines by two obstetricians. Multivariable models were constructed to control for confounders. Variable decelerations, late decelerations and bradycardia during the 1st and 2nd stages of labor were significantly higher in group of deliveries ended in cord pH < 7.2 compared with group of deliveries ended in cord pH > 7.2. A significant association was observed between category 2 and 3 during the 1st stage of labor and pH ≤ 7.2. However, while controlling for FHR category 3 at the 2nd stage of labor, 1st stage categorization lost its association with pH <7.2, and only category 3 during the 2nd stage were noted as an independent risk factor for acidosis. FHR monitoring category 3 during the 2nd stage of labor is an independent predictor of fetal acidosis as expressed by arterial cord pH < 7.2.

  8. Processing of fetal heart rate through non-invasive adaptive system based on recursive least squares algorithm

    NASA Astrophysics Data System (ADS)

    Fajkus, Marcel; Nedoma, Jan; Martinek, Radek; Vasinek, Vladimir

    2017-10-01

    In this article, we describe an innovative non-invasive method of Fetal Phonocardiography (fPCG) using fiber-optic sensors and adaptive algorithm for the measurement of fetal heart rate (fHR). Conventional PCG is based on a noninvasive scanning of acoustic signals by means of a microphone placed on the thorax. As for fPCG, the microphone is placed on the maternal abdomen. Our solution is based on patent pending non-invasive scanning of acoustic signals by means of a fiber-optic interferometer. Fiber-optic sensors are resistant to technical artifacts such as electromagnetic interferences (EMI), thus they can be used in situations where it is impossible to use conventional EFM methods, e.g. during Magnetic Resonance Imaging (MRI) examination or in case of delivery in water. The adaptive evaluation system is based on Recursive least squares (RLS) algorithm. Based on real measurements provided on five volunteers with their written consent, we created a simplified dynamic signal model of a distribution of heartbeat sounds (HS) through the human body. Our created model allows us to verification of the proposed adaptive system RLS algorithm. The functionality of the proposed non-invasive adaptive system was verified by objective parameters such as Sensitivity (S+) and Signal to Noise Ratio (SNR).

  9. Fetal Heart Rate Monitoring during Intrauterine Open Surgery for Myelomeningocele Repair.

    PubMed

    Santana, Eduardo Félix Martins; Moron, Antônio Fernandes; Barbosa, Maurício Mendes; Milani, Herbene Jose Figuinha; Sarmento, Stephanno Gomes Pereira; Araujo Júnior, Edward; Rolo, Liliam Cristine; Cavalheiro, Sérgio

    2016-01-01

    The aim of this study was to assess fetal hemodynamics during intrauterine open surgery for myelomeningocele (MMC) repair by describing fetal heart rate (FHR) monitoring in detail related to each part of the procedure. A study was performed with 57 fetuses submitted to intrauterine MMC repair between the 24th and 27th week of gestation. Evaluations of FHR were made in specific periods: before anesthesia, after anesthesia, at the beginning of laparotomy, during uterus abdominal withdrawal, hysterotomy, neurosurgery (before incision, during early skin manipulation, spinal cord releasing, and at the end of neurosurgery), abdominal cavity reintroduction, and abdominal closure, and at the end of surgery. Means ± standard deviations of FHR were established for each period, and analysis of variance with repeated measures was used to assess differences between these periods. The mean differences were assessed with 95% confidence intervals and were analyzed by Tukey's multiple comparison test. The mean FHR during the specific periods mentioned above was 140.2, 140, 139.2, 138.8, 135.1, 133.9, 123.1, 134.0, 134.5, 137.9, and 139.9 bpm, respectively (p < 0.0001). Comparing the different periods, the highest frequencies were observed in the initial and final moments. The neurosurgery stage presents lower frequencies, especially during the release of the spinal cord. FHR monitoring revealed interesting findings in terms of physiological fetal changes during MMC repair, especially during neurosurgery, which was the most critical period. © 2015 S. Karger AG, Basel.

  10. Minimally Invasive Implantable Fetal Micropacemaker: Mechanical Testing and Technical Refinements

    PubMed Central

    Zhou, Li; Vest, Adriana N.; Peck, Raymond A.; Sredl, Jonathan P.; Huang, Xuechen; Bar-Cohen, Yaniv; Silka, Michael J.; Pruetz, Jay D.; Chmait, Ramen H.; Loeb, Gerald E.

    2016-01-01

    This paper discusses the technical and safety requirements for cardiac pacing of a human fetus with heart failure and hydrops fetalis secondary to complete heart block. Engineering strategies to meet specific technical requirements were integrated into a systematic design and implementation consisting of a novel fetal micropacemaker, a percutaneous implantation system, and a sterile package that enables device storage and recharging maintenance in a clinical setting. We further analyzed observed problems on myocardial fixation and pacing lead fatigue previously reported in earlier preclinical trials. This paper describes the technical refinements of the implantable fetal micropacemaker to overcome these challenges. The mechanical performance has been extensively tested to verify the improvement of reliability and safety margins of the implantation system. PMID:27021067

  11. Development of the peptidergic innervation of human heart.

    PubMed Central

    Gordon, L; Polak, J M; Moscoso, G J; Smith, A; Kuhn, D M; Wharton, J

    1993-01-01

    The aim of the present investigation was to study the developing peptidergic innervation of the human fetal heart of 7-24 wk gestational age. An immunohistochemical approach was adopted and the total innervation visualised with antisera to general neuronal and Schwann cell markers, while the onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP). Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas peptide-immunoreactive nerves were not observed until the 10th week of gestation. NPY-immunoreactive nerve fibres constituted the major subpopulation of peptide-containing nerves identified in the fetal heart, exhibiting a descending atrial to ventricular density gradient, and were first identified during the 10th wk of gestation. Somatostatin- and VIP-immunoreactive nerves appeared at 10-12 wk of gestation and were mainly distributed in the atria. Somatostatin immunoreactivity was localised to cell bodies in cardiac ganglia, as well as to nerve fibres, indicating an intrinsic origin for this nerve subpopulation. Conversely, the other peptide-containing nerves appear to be of extrinsic origin, including those immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of tyrosine hydroxylase immunoreactivity. Putative sympathetic nerve fibres, displaying tyrosine hydroxylase and NPY immunoreactivity, were demonstrated before the adrenergic innervation has previously been shown to be present by formaldehyde-induced fluorescence staining of catecholamines. The onset of the CGRP- and SP-immunoreactive innervation, at 18-24 wk of gestation, followed the appearance of other peptide-containing nerves, suggesting that the sensory, afferent innervation occurs later than the autonomic. The differential appearance and distribution of peptide

  12. A brief history of fetal echocardiography and its impact on the management of congenital heart disease.

    PubMed

    Maulik, Dev; Nanda, Navin C; Maulik, Devika; Vilchez, Gustavo

    2017-12-01

    Congenital heart disease (CHD), the most common congenital malformation, is associated with adverse outcome. Development of fetal echocardiography has made prenatal diagnosis of CHD a reality, and in the process revolutionized its management. This historical review briefly narrates this development over the decades focusing on the emergence of the primary modalities of fetal echocardiography comprised of the time-motion mode, two-dimensional B-mode, spectral Doppler, color Doppler, and three- and four-dimensional cardiac imaging. Collaboration between clinicians and engineers has been central to these advances. Also discussed are the accuracy and impact of fetal echocardiography on the management of CHD, and especially its role in the prenatal diagnosis of critical CHD in individualizing the management and improving the outcome. Despite these advances, most cases of CHD are not identified prenatally, emphasizing the continuing need for further technological and educational innovation and improvement. © 2017, Wiley Periodicals, Inc.

  13. Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

    PubMed

    Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M

    2007-03-15

    Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

  14. Sex-related differences in the development of fetal heart rate dynamics.

    PubMed

    Kim, Kyu Nam; Park, Young-Sun; Hoh, Jeong-Kyu

    2016-02-01

    Despite previous efforts to explain the general advantages of female fetuses over males regarding health, sex-related differences in the dynamics or complexity of fetal heart rate (FHR) variability and FHR maturation patterns have not yet been identified. To make linear and nonlinear comparisons of antepartum FHR indices, dynamics, complexity, and reactivity to the non-stress test (NST) and vibroacoustic-stimulation test (VAST) in male and female fetuses. A total of 3835 singleton term deliveries without maternal and fetal complications were divided into female (n=1849) and male (n=1986) groups, and subjected to comparison and analyses. Linear FHR indices, approximate entropy (ApEn), sample entropy (SampEn), short-term/long-term exponents (α1/α2), correlation dimension (CD), NST and VAST criteria, and modified nonlinear reactive criteria (MNRC) were used to evaluate outcomes. ApEn was consistently higher in female fetuses than in male ones. ApEn in female fetuses was maximal at 29-30 gestational weeks, while the increase in ApEn was delayed in male fetuses but more rapid, reaching its peak at 31-32 gestational weeks. In both sexes, CD increased up to term, and α2 rapidly decreased up to 31-32weeks in an analogous manner. The two sexes differed significantly in response to VAST at <31 gestational weeks and there was a structural difference in reactive patterns under MNRC. Female fetuses exhibit greater heart rate dynamics in early gestational periods, suggesting that their cardiovascular system matures earlier than that of males. Male fetuses undergo a compensatory period of rapid change to catch up with females at term. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR

    PubMed Central

    Brennan, Sarah C.; Wilkinson, William J.; Tseng, Hsiu-Er; Finney, Brenda; Monk, Bethan; Dibble, Holly; Quilliam, Samantha; Warburton, David; Galietta, Luis J.; Kemp, Paul J.; Riccardi, Daniela

    2016-01-01

    Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory diseases. PMID:26911344

  16. Identification of CYP3A7 for Glyburide Metabolism in Human Fetal Livers

    PubMed Central

    Shuster, Diana L.; Risler, Linda J.; Prasad, Bhagwat; Calamia, Justina C.; Voellinger, Jenna L.; Kelly, Edward J.; Unadkat, Jashvant D.; Hebert, Mary F.; Shen, Danny D.; Thummel, Kenneth E.; Mao, Qingcheng

    2014-01-01

    Glyburide is commonly prescribed for the treatment of gestational diabetes mellitus; however, fetal exposure to glyburide is not well understood and may have short- and long-term consequences for the health of the child. Glyburide can cross the placenta; fetal concentrations at term are nearly comparable to maternal levels. Whether or not glyburide is metabolized in the fetus and by what mechanisms has yet to be determined. In this study, we determined the kinetic parameters for glyburide depletion by CYP3A isoenzymes; characterized glyburide metabolism by human fetal liver tissues collected during the first or early second trimester of pregnancy; and identified the major enzyme responsible for glyburide metabolism in human fetal livers. CYP3A4 had the highest metabolic capacity towards glyburide, followed by CYP3A7 and CYP3A5 (Clint,u = 37.1, 13.0, and 8.7 ml/min/nmol P450, respectively). M5 was the predominant metabolite generated by CYP3A7 and human fetal liver microsomes (HFLMs) with approximately 96% relative abundance. M5 was also the dominant metabolite generated by CYP3A4, CYP3A5, and adult liver microsomes; however, M1-M4 were also present, with up to 15% relative abundance. CYP3A7 protein levels in HFLMs were highly correlated with glyburide Clint, 16α-OH DHEA formation, and 4′-OH midazolam formation. Likewise, glyburide Clint was highly correlated with 16α-OH DHEA formation. Fetal demographics as well as CYP3A5 and CYP3A7 genotype did not alter CYP3A7 protein levels or glyburide Clint. These results indicate that human fetal livers metabolize glyburide predominantly to M5 and that CYP3A7 is the major enzyme responsible for glyburide metabolism in human fetal livers. PMID:25450675

  17. Identification of CYP3A7 for glyburide metabolism in human fetal livers.

    PubMed

    Shuster, Diana L; Risler, Linda J; Prasad, Bhagwat; Calamia, Justina C; Voellinger, Jenna L; Kelly, Edward J; Unadkat, Jashvant D; Hebert, Mary F; Shen, Danny D; Thummel, Kenneth E; Mao, Qingcheng

    2014-12-15

    Glyburide is commonly prescribed for the treatment of gestational diabetes mellitus; however, fetal exposure to glyburide is not well understood and may have short- and long-term consequences for the health of the child. Glyburide can cross the placenta; fetal concentrations at term are nearly comparable to maternal levels. Whether or not glyburide is metabolized in the fetus and by what mechanisms has yet to be determined. In this study, we determined the kinetic parameters for glyburide depletion by CYP3A isoenzymes; characterized glyburide metabolism by human fetal liver tissues collected during the first or early second trimester of pregnancy; and identified the major enzyme responsible for glyburide metabolism in human fetal livers. CYP3A4 had the highest metabolic capacity towards glyburide, followed by CYP3A7 and CYP3A5 (Clint,u=37.1, 13.0, and 8.7ml/min/nmol P450, respectively). M5 was the predominant metabolite generated by CYP3A7 and human fetal liver microsomes (HFLMs) with approximately 96% relative abundance. M5 was also the dominant metabolite generated by CYP3A4, CYP3A5, and adult liver microsomes; however, M1-M4 were also present, with up to 15% relative abundance. CYP3A7 protein levels in HFLMs were highly correlated with glyburide Clint, 16α-OH DHEA formation, and 4'-OH midazolam formation. Likewise, glyburide Clint was highly correlated with 16α-OH DHEA formation. Fetal demographics as well as CYP3A5 and CYP3A7 genotype did not alter CYP3A7 protein levels or glyburide Clint. These results indicate that human fetal livers metabolize glyburide predominantly to M5 and that CYP3A7 is the major enzyme responsible for glyburide metabolism in human fetal livers. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Change of Spectral Analysis of Fetal Heart Rate During Clinical Hypnosis: a Prospective Randomised Trial from the 20th Week of Gestation Till Term

    PubMed Central

    Reinhard, J.; Hayes-Gill, B. R.; Schiermeier, S.; Hatzmann, W.; Heinrich, T. M.; Hüsken-Janßen, H.; Herrmann, E.; Louwen, F.

    2012-01-01

    Objective: To investigate the functional adaptive process of the fetal autonomic nervous system during hypnosis from the 20th week of gestation till term. Are there changes in the power spectrum analysis of fetal heart rate when the mother is having a clinical hypnosis or control period? Study Design: Fourty-nine FHR recordings were analysed. Included recordings were from singletons and abdominal fetal ECG-monitored pregnancies. All women were randomised to receive clinical hypnosis followed by a period with no intervention or vice versa. Statistical analyses were performed with the Wilcoxon signed ranks and Spearman rho correlation tests. Results: There was a significant difference found between fetal heart rate at baseline (144.3 ± 6.0) and hypnosis (142.1 ± 6.4). A difference was also detected between the standard deviation of the heart rate between baseline (6.7 ± 1.9) and hypnosis (6.8 ± 3.5). LFnu was smaller during baseline (80.2 ± 5.3) than during hypnosis (82.1 ± 5.7), whereas HFnu was significantly larger (19.8 ± 5.3 vs. 17.9 ± 5.7). There was no correlation between the gestation age and the change in LFnu, HFnu or ratio LF/HF due to the hypnosis intervention. Conclusion: The functional adaptive process of the fetal autonomic system during hypnosis is reflected by a sympathovagal shift towards increased sympathetic modulation. PMID:25284838

  19. A Prospective Study of the Use of Fetal Intelligent Navigation Echocardiography (FINE) to Obtain Standard Fetal Echocardiography Views

    PubMed Central

    Veronese, Paola; Bogana, Gianna; Cerutti, Alessia; Yeo, Lami; Romero, Roberto; Gervasi, Maria Teresa

    2016-01-01

    Objective To evaluate the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart in generating standard fetal echocardiography views. Methods In this prospective cohort study of patients with normal fetal hearts (19-30 gestational weeks), one or more STIC volume datasets were obtained of the apical four-chamber view. Each STIC volume successfully obtained was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates for standard fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. Results One or more STIC volumes (n=463 total) were obtained in 246 patients. A single STIC volume per patient was analyzed using the FINE method. In normal cases, FINE was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 76-100% of cases; 2) VIS-Assistance® in 96-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance® in 96-100% of cases. Conclusion FINE applied to STIC volumes can successfully generate nine standard fetal echocardiography views in 96-100% of cases in the second and third trimesters. This suggests that the technology can be used as a method to screen for congenital heart disease. PMID:27309391

  20. Fetal motion estimation from noninvasive cardiac signal recordings.

    PubMed

    Biglari, Hadis; Sameni, Reza

    2016-11-01

    Fetal motility is a widely accepted indicator of the well-being of a fetus. In previous research, it has be shown that fetal motion (FM) is coherent with fetal heart rate accelerations and an indicator for active/rest cycles of the fetus. The most common approach for FM and fetal heart rate (FHR) assessment is by Doppler ultrasound (DUS). While DUS is the most common approach for studying the mechanical activities of the heart, noninvasive fetal electrocardiogram (ECG) and magnetocardiogram (MCG) recording and processing techniques have been considered as a possible competitor (or complement) for the DUS. In this study, a fully automatic and robust framework is proposed for the extraction, ranking and alignment of fetal QRS-complexes from noninvasive fetal ECG/MCG. Using notions from subspace tracking, two measures, namely the actogram and rotatogram, are defined for fetal motion tracking. The method is applied to four fetal ECG/MCG databases, including twin MCG recordings. By defining a novel measure of causality, it is shown that there is significant coherency and causal relationship between the actogram/rotatogram and FHR accelerations/decelerations. Using this measure, it is shown that in many cases, the actogram and rotatogram precede the FHR variations, which supports the idea of motion-induced FHR accelerations/decelerations for these cases and raises attention for the non-motion-induced FHR variations, which can be associated to the fetal central nervous system developments. The results of this study can lead to novel perspectives of the fetal sympathetic and parasympathetic brain systems and future requirements of fetal cardiac monitoring.

  1. Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy

    PubMed Central

    Ames, EG; Lawson, MJ; Mackey, AJ; Holmes, JW

    2013-01-01

    Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are reexpressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (P < 0.001). The isoforms that are shared between hypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development. PMID:23688780

  2. Isolation, culture, and imaging of human fetal pancreatic cell clusters.

    PubMed

    Lopez, Ana D; Kayali, Ayse G; Hayek, Alberto; King, Charles C

    2014-05-18

    For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning endocrine cells, as evidenced by a significant increase in circulating human C-peptide following glucose stimulation(1-9). However in vitro, genesis of insulin producing cells from human fetal ICCs is low(10); results reminiscent of recent experiments performed with human embryonic stem cells (hESC), a renewable source of cells that hold great promise as a potential therapeutic treatment for type 1 diabetes. Like ICCs, transplantation of partially differentiated hESC generate glucose responsive, insulin producing cells, but in vitro genesis of insulin producing cells from hESC is much less robust(11-17). A complete understanding of the factors that influence the growth and differentiation of endocrine precursor cells will likely require data generated from both ICCs and hESC. While a number of protocols exist to generate insulin producing cells from hESC in vitro(11-22), far fewer exist for ICCs(10,23,24). Part of that discrepancy likely comes from the difficulty of working with human fetal pancreas. Towards that end, we have continued to build upon existing methods to isolate fetal islets from human pancreases with gestational ages ranging from 12 to 23 weeks, grow the cells as a monolayer or in suspension, and image for cell proliferation, pancreatic markers and human hormones including glucagon and C-peptide. ICCs generated by the protocol described below result in C-peptide release after transplantation under the kidney capsule of nude mice that are similar to C-peptide levels obtained by transplantation of fresh tissue(6). Although the examples presented here focus upon the pancreatic endoderm proliferation and β cell genesis, the protocol can be employed to study other aspects of pancreatic development, including exocrine, ductal, and other hormone producing cells.

  3. Fetal short time variation during labor: a non-invasive alternative to fetal scalp pH measurements?

    PubMed

    Schiermeier, Sven; Reinhard, Joscha; Hatzmann, Hendrike; Zimmermann, Ralf C; Westhof, Gregor

    2009-01-01

    To determine whether short time variation (STV) of fetal heart beat correlates with scalp pH measurements during labor. From 1279 deliveries, 197 women had at least one fetal scalp pH measurement. Using the CTG-Player, STVs were calculated from the electronically saved cardiotocography (CTG) traces and related to the fetal scalp pH measurements. There was no correlation between STV and fetal scalp pH measurements (r=-0.0592). Fetal STV is an important parameter with high sensitivity for antenatal fetal acidosis. This study shows that STV calculations do not correlate with fetal scalp pH measurements during labor, hence are not helpful in identifying fetal acidosis.

  4. Prenatally fabricated autologous human living heart valves based on amniotic fluid derived progenitor cells as single cell source.

    PubMed

    Schmidt, Dörthe; Achermann, Josef; Odermatt, Bernhard; Breymann, Christian; Mol, Anita; Genoni, Michele; Zund, Gregor; Hoerstrup, Simon P

    2007-09-11

    A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced. Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133- and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133- derived cells were seeded onto heart valve leaflet scaffolds (n=18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133- derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions. The use of amniotic fluid as single cell source is a promising low-risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations.

  5. Cephalometric assessment of human fetal head specimens.

    PubMed

    Radlanski, R J; Heikinheimo, K; Gruda, A

    2013-07-01

    Past investigations of prenatal craniofacial growth have largely relied on histological sections. Few studies have taken measurements on three-dimensional representations (3D reconstruction, 3D CT, postmortem) or varying depth levels (ultrasound), and we know of no craniofacial growth studies done on cleared-and-stained specimens of whole fetal heads. This study comprised 14 human fetal head specimens cleared and stained with alizarin red and alcian blue. They had been stored in glycerol and represented weeks 8-12 of gestation, with crown-rump lengths ranging from 23-145 mm. These specimens were cephalometrically analyzed in norma frontalis and norma lateralis, which notably included the opportunity for side-to-side comparison. As the cranial membrane bones progressively approached each other, the orbits, maxilla, and mandible gradually grew wider. Likewise, the sagittal dimensions of the maxilla and mandible increased continuously and synchronically. We noted side-to-side differences ranging from 2-5 mm. Another notable finding concerned the inclination of the maxilla relative to the cranial base, which increased more on the right than on the left side. This is the first investigation presenting side-to-side comparative measurements of human fetal head specimens. Such measurements are essential in the quest toward validating the findings of other imaging techniques such as CT or MRI and-most importantly-intrauterine sonography.

  6. Nonlinear analysis of heart rate variability to assess the reaction of ewe fetuses undergoing fetal cardiac surgery.

    PubMed

    Del Gaudio, Costantino; Carotti, Adriano; Grigioni, Mauro; Morbiducci, Umberto

    2012-05-01

    Fetal cardiac surgery (FCS) represents a challenging issue for the in utero treatment of congenital heart defects. However, FCS has still not gained the sufficient reliability for clinical practice due to an incompletely elucidated fetal stress response. For example, blood sampling can contribute to its onset, leading to fetoplacental unit dysfunction, one of the main causes of failure of the surgical procedure. In order to address this issue, the role of the autonomic control system during an experimental procedure of cardiac bypass on ewe fetuses was investigated by means of recurrence quantification analysis (RQA), a well-recognized method for the analysis of nonlinear systems. RQA was applied to time series extracted from fetal arterial pressure recordings before and after the cardiac bypass established by means of an extracorporeal circuit, including an axial blood pump, and taking advantage of the capability of the placenta to work as a natural oxygenator. Statistically significant correlations were found among RQA-based metrics and fetal blood gas data, suggesting the possibility to infer the clinical status of the fetus starting from its hemodynamic signals.This study shows the relevance of RQA as a complementary tool for the monitoring of the fetal status during cardiac bypass.

  7. Maternal positioning affects fetal heart rate changes after epidural analgesia for labour.

    PubMed

    Preston, R; Crosby, E T; Kotarba, D; Dudas, H; Elliott, R D

    1993-12-01

    Adverse fetal heart rate (FHR) changes suggestive of fetal hypoxia are seen in patients with normal term pregnancies after initiation of epidural block for labour analgesia. It was our hypothesis that, in some parturients, these changes were a consequence of concealed aortocaval compression resulting in decreased uterine blood flow. We expected that the full lateral position compared with the wedged supine position would provide more effective prophylaxis against aortocaval compression. To test our hypothesis we studied the role of maternal positioning on FHR changes during onset of epidural analgesia for labour. Eighty-eight ASA Class I or II term parturients were randomized into two groups: those to be nursed in the wedged supine position and those to be nursed in the full lateral position during induction of an epidural block. External FHR monitoring was employed to assess the fetal response to initiation of labour epidural analgesia. Epidural catheters were sited with the parturients in the sitting position and the patients then assumed the study position. After a negative test dose, a standardized regimen of bupivacaine 0.25% was employed to provide labour analgesia. The quality and efficacy of the block were assessed using VAS pain scores, motor block scores and sensory levels. The results demonstrated that there was no difference in the quality of analgesia provided nor in the incidence of asymmetric blocks. There was no difference in the observed incidence of FHR changes occurring during the initiation of the epidural block.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. The rhetoric of informed choice: perspectives from midwives on intrapartum fetal heart rate monitoring

    PubMed Central

    Hindley, Carol; Thomson, Ann M.

    2005-01-01

    Abstract Objective  To investigate midwives’ attitudes, values and beliefs on the use of intrapartum fetal monitoring. Design  Qualitative, semi‐structured interviews Subjects and setting  Fifty‐eight registered midwives in two hospitals in the North of England. Results  In this paper two main themes are discussed, these are: informed choice, and the power of the midwife. Midwives favoured the application of informed choice and shared a unanimous consensus on the definition. However, the idealistic perception of informed choice, which included contemporary notions of empowerment and autonomy for women expressing an informed choice, was not reportedly translated into practice. Midwives had to implement informed choice on intrapartum fetal monitoring within a competing set of health service agendas, i.e. medically driven protocols and a political climate of actively managed childbearing. This resulted in the manipulation of information during the midwives’ interactions with women. This ultimately meant that the women often got the choice the midwives wanted them to have. Conclusions  The information that a midwife imparts may consciously or subconsciously affect the woman's uptake and understanding of information. Therefore, the midwife has a powerful role to play in balancing the benefits and risk ratios applicable to fetal heart rate monitoring. However, a deeply ingrained pre‐occupation with technological methods of intrapartum fetal monitoring over many years has made it difficult for midwives to offer alternative forms of monitoring. This has placed limits on the facilitation of informed choice and autonomous decision making for women. PMID:16266418

  9. Telemetric monitoring of fetal blood pressure and heart rate in the freely moving pregnant sheep: a feasibility study.

    PubMed

    Abi-Nader, Khalil N; Mehta, Vedanta; Shaw, S W Steven; Bellamy, Tom; Smith, Neil; Millross, Laura; Laverick, Beth; Filippi, Elisa; Boyd, Michael; Peebles, Donald M; David, Anna L

    2011-01-01

    Remote telemetric monitoring of fetal haemodynamics in pregnant sheep would allow unrestricted animal movement, minimize suffering and distress, and improve animal welfare, while enhancing the quality of data collected. This may also be useful in clinical practice following fetal surgery. Using an open fetal surgical technique at approximately two-thirds of gestation, we implanted the catheter of a D70-PCTP haemodynamic telemetric device (Data Sciences International, Tilburg, The Netherlands) into the carotid artery of the fetal sheep (n = 4). The attached transmitter was secured to the posterior aspect of the maternal anterior abdominal wall. Two receivers, with a range of 1 m each, were sited in an 11 m² sheep enclosure to maximize animal freedom while allowing continuous monitoring of the ewe. The receivers were connected by cable to a nearby computer. In the first two procedures, both fetuses died eight and 12 days after surgery, and the catheter tip was observed to be lying in the bicarotid trunk. In the next two procedures the catheter tip was threaded further upstream from the insertion point, in an attempt to reach the fetal aorta, and both fetuses survived until the scheduled postmortem examination at the end of pregnancy. After catheter implantation, fetal blood pressure (BP) and heart rate (HR) were successfully recorded continuously for seven days and then hourly per day for a further three weeks. The fetal BP and HR values were in the normal range for healthy sheep fetuses.

  10. Altered autonomic control of heart rate variability in the chronically hypoxic fetus.

    PubMed

    Shaw, C J; Allison, B J; Itani, N; Botting, K J; Niu, Y; Lees, C C; Giussani, D A

    2018-03-31

    Fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, and a decrease in FHRV is associated with fetal compromise. However, the mechanisms by which FHRV is reduced in the chronically hypoxic fetus have yet to be established. The sympathetic and parasympathetic influences on heart rate mature at different rates throughout fetal life, and can be assessed by time domain and power spectral analysis of FHRV. In this study of chronically instrumented fetal sheep in late gestation, we analysed FHRV daily over a 16 day period towards term, and compared changes between fetuses of control and chronically hypoxic pregnancy. We show that FHRV in sheep is reduced by chronic hypoxia, predominantly due to dysregulation of the sympathetic control of the fetal heart rate. This presents a potential mechanism by which a reduction in indices of FHRV predicts fetuses at increased risk of neonatal morbidity and mortality in humans. Reduction in overall FHRV may therefore provide a biomarker that autonomic dysregulation of fetal heart rate control has taken place in a fetus where uteroplacental dysfunction is suspected. Although fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, the mechanisms by which it is reduced in the chronically hypoxic fetus have yet to be established. In particular, the physiological mechanism underlying the reduction of short term variation (STV) in fetal compromise remains unclear. In this study, we present a longitudinal study of the development of autonomic control of FHRV, assessed by indirect indices, time domain and power spectral analysis, in normoxic and chronically hypoxic, chronically catheterised, singleton fetal sheep over the last third of gestation. We used isobaric chambers able to maintain pregnant sheep for prolonged periods in hypoxic conditions (stable fetal femoral arterial PO2 10-12 mmHg), and a customised wireless data acquisition

  11. Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

    PubMed

    Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

    1999-05-01

    Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

  12. A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model.

    PubMed

    Garabedian, C; Champion, C; Servan-Schreiber, E; Butruille, L; Aubry, E; Sharma, D; Logier, R; Deruelle, P; Storme, L; Houfflin-Debarge, V; De Jonckheere, J

    2017-01-01

    Analysis of heart rate variability (HRV) is a recognized tool in the assessment of autonomic nervous system (ANS) activity. Indeed, both time and spectral analysis techniques enable us to obtain indexes that are related to the way the ANS regulates the heart rate. However, these techniques are limited in terms of the lack of thresholds of the numerical indexes, which is primarily due to high inter-subject variability. We proposed a new fetal HRV analysis method related to the parasympathetic activity of the ANS. The aim of this study was to evaluate the performance of our method compared to commonly used HRV analysis, with regard to i) the ability to detect changes in ANS activity and ii) inter-subject variability. This study was performed in seven sheep fetuses. In order to evaluate the sensitivity and specificity of our index in evaluating parasympathetic activity, we directly administered 2.5 mg intravenous atropine, to inhibit parasympathetic tone, and 5 mg propranolol to block sympathetic activity. Our index, as well as time analysis (root mean square of the successive differences; RMSSD) and spectral analysis (high frequency (HF) and low frequency (LF) spectral components obtained via fast Fourier transform), were measured before and after injection. Inter-subject variability was estimated by the coefficient of variance (%CV). In order to evaluate the ability of HRV parameters to detect fetal parasympathetic decrease, we also estimated the effect size for each HRV parameter before and after injections. As expected, our index, the HF spectral component, and the RMSSD were reduced after the atropine injection. Moreover, our index presented a higher effect size. The %CV was far lower for our index than for RMSSD, HF, and LF. Although LF decreased after propranolol administration, fetal stress index, RMSSD, and HF were not significantly different, confirming the fact that those indexes are specific to the parasympathetic nervous system. In conclusion, our method

  13. The effect of spinal hyperbaric bupivacaine-fentanyl or hyperbaric bupivacaine on uterine tone and fetal heart rate in labouring women: a randomised controlled study.

    PubMed

    Kuberan, A; Jain, K; Bagga, R; Makkar, J K

    2018-07-01

    The mechanism for fetal heart rate abnormalities following spinal opioids remains controversial. We evaluated uterine tone, using an intra-uterine pressure catheter, and fetal heart rate abnormalities in 30 women in spontaneous labour with cervical dilation of 3-5 cm having combined spinal-epidural analgesia. Women were randomly assigned to receive a spinal with 2.0 mg hyperbaric bupivacaine plus 15 μg fentanyl, or 2.5 mg hyperbaric bupivacaine. The primary outcome measure was an increase > 10 mmHg in baseline uterine tone in the 30-min period following spinal injection. Only three (20%) women who had a bupivacaine-fentanyl spinal showed a > 10 mmHg increase in baseline tone vs. none who had bupivacaine (p = 0.63). The mean (SD) baseline uterine tone after the spinal injection was 13.3 (7.0) mmHg in the bupivacaine-fentanyl group and 7.7 (2.5) mmHg in the bupivacaine group (p = 0.01). Seven (47%) in the bupivacaine-fentanyl group showed new onset fetal heart rate changes during the 30-min period after the spinal, compared with two (13%) in the bupivacaine group (p = 0.04); however, these were transient and responded to intra-uterine resuscitation. Pain scores, sensory and motor block as well as neonatal outcomes were comparable between the groups. We found that raised baseline uterine tone was not more frequent when using bupivacaine-fentanyl rather than bupivacaine in the spinal component of combined spinal-epidural, although absolute values of baseline tone were higher, and fetal heart rate changes more frequent, in the former group. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  14. Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

    PubMed

    Holm, Maia Blomhoff; Bastani, Nasser Ezzatkhah; Holme, Ane Moe; Zucknick, Manuela; Jansson, Thomas; Refsum, Helga; Mørkrid, Lars; Blomhoff, Rune; Henriksen, Tore; Michelsen, Trond Melbye

    2017-01-01

    The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample. This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations. In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake. Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the

  15. Human Fetal Membranes at Term: Dead Tissue or Signalers of Parturition?

    PubMed Central

    MENON, Ramkumar

    2017-01-01

    Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging. Fetal membrane senescence is also allied with completion of fetal maturation at term as the fetus readies for delivery, which may also indicate the end of independent life and longevity of fetal membranes as their functional role concludes. Fetal membrane senescence is accelerated at term because of oxidative stress and increased stretching. Senescent fetal membranes cells produce senescence-associated secretory phenotype (SASP-inflammation) and also release proinflammatory damage-associated molecular patterns (DAMPs), namely HMGB1 and cell-free fetal telomere fragments. In a feedback loop, SASP and DAMPs increase senescence and enhance the inflammatory load to promote labor. Membranes increase the inflammatory load to disrupt homeostatic balance to transition quiescent uterine tissues toward a labor phenotype. Therefore, along with other well-described labor-promoting signals, senescent fetal membranes may also contribute to human term parturition. PMID:27452431

  16. Telefetalcare: a first prototype of a wearable fetal electrocardiograph.

    PubMed

    Fanelli, A; Signorini, M G; Ferrario, M; Perego, P; Piccini, L; Andreoni, G; Magenes, G

    2011-01-01

    Fetal heart rate monitoring is fundamental to infer information about fetal health state during pregnancy. The cardiotocography (CTG) is the most common antepartum monitoring technique. Abdominal ECG recording represents the most valuable alternative to cardiotocography, as it allows passive, non invasive and long term fetal monitoring. Unluckily fetal ECG has low SNR and needs to be extracted from abdominal recordings using ad hoc algorithms. This work describes a prototype of a wearable fetal ECG electrocardiograph. The system has flat band frequency response between 1-60 Hz and guarantees good signal quality. It was tested on pregnant women between the 30(th) and 34(th) gestational week. Several electrodes configurations were tested, in order to identify the best solution. Implementation of a simple algorithm for FECG extraction permitted the reliable detection of maternal and fetal QRS complexes. The system will allow continuative and deep screening of fetal heart rate, introducing the possibility of home fetal monitoring.

  17. A novel route of transplantation of human cord blood stem cells in preimmune fetal sheep: the intracelomic cavity.

    PubMed

    Noia, Giuseppe; Pierelli, Luca; Bonanno, Giuseppina; Monego, Giovanni; Perillo, Alessandro; Rutella, Sergio; Cavaliere, Anna Franca; De Santis, Marco; Ligato, Maria Serena; Fortunato, Giuseppe; Scambia, Giovanni; Terzano, Giuseppina Maria; Iannace, Enrico; Zelano, Giovanni; Michetti, Fabrizio; Leone, Giuseppe; Mancuso, Salvatore; Terzano, Marinela; Fotunato, Giuseppe

    2003-01-01

    The intracelomic route for in utero hematopoietic stem cell transplantation was evaluated in preimmune fetal sheep and the engraftment characteristics were defined. Twelve twin ovine fetuses (gestational age: 40-45 days) received intracelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34-selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses of human beta2-microglobulin. Four fetuses (33%) aborted shortly after intracelomic transplantation and were not evaluable for engraftment. Engraftment was detected in four fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degrees of engraftment in these four fetuses ranged from 6%-22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days and one fetus delivered at term that received CD34-selected cord blood cells had human engraftment with 10%, 32%, 20%, and 10% CD45(+) cells in bone marrow, respectively. In six of eight fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human beta2-microglobulin, which also identified human cells in brain, spinal cord, heart, lung, and skeletal muscle. This preliminary study indicates that intracelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.

  18. Human fetal membranes at term: Dead tissue or signalers of parturition?

    PubMed

    Menon, Ramkumar

    2016-08-01

    Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging. Fetal membrane senescence is also allied with completion of fetal maturation at term as the fetus readies for delivery, which may also indicate the end of independent life and longevity of fetal membranes as their functional role concludes. Fetal membrane senescence is accelerated at term because of oxidative stress and increased stretching. Senescent fetal membranes cells produce senescence-associated secretory phenotype (SASP-inflammation) and also release proinflammatory damage-associated molecular patterns (DAMPs), namely HMGB1 and cell-free fetal telomere fragments. In a feedback loop, SASP and DAMPs increase senescence and enhance the inflammatory load to promote labor. Membranes increase the inflammatory load to disrupt homeostatic balance to transition quiescent uterine tissues toward a labor phenotype. Therefore, along with other well-described labor-promoting signals, senescent fetal membranes may also contribute to human term parturition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Intrapartum fetal heart rate patterns of trisomy 21 fetuses: A case-control study.

    PubMed

    Koren, Inbal; Michaelson-Cohen, Rachel; Chen, Daniela; Michaeli, Jennia; Schimmel, Michael; Tsafrir, Avi; Shen, Ori

    2016-01-01

    To determine whether there are specific characteristic intrapartum heart rate patterns for fetuses with trisomy 21(T21). Intrapartum fetal heart rate (FHR) tracings of T21 fetuses were compared to those of euploid fetuses in a retrospective, observational, matched, case-control study. The study group consisted of 42 fetuses with T21 and 42 matched euploid controls. Matching was designed to accommodate possible confounders. The sign test and McNemar's test were used for categorical variables. The paired t test was used for comparison between quantitative variables. Intrapartum baseline FHR of fetuses with T21 was found to be slightly decreased compared to controls (122.5 vs 129.05 beats per minute, p=0.028). No differences were detected in the presence of periodic changes, or FHR variability between the groups. When evaluating intrapartum FHR of fetuses with T21, decreased baseline FHR can be expected. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Impact of gestational chronodisruption on fetal cardiac genomics.

    PubMed

    Galdames, Hugo A; Torres-Farfan, Claudia; Spichiger, Carlos; Mendez, Natalia; Abarzua-Catalan, Lorena; Alonso-Vazquez, Pamela; Richter, Hans G

    2014-01-01

    We recently reported that gestational chronodisruption induces fetal growth restriction and marked effects on fetal adrenal physiology. Here, whole-transcriptome profiling was used to test whether gestational chronodisruption modifies gene expression in the fetal heart, potentially altering cardiac development. At day 10 of gestation (E10), pregnant rats were randomized in two groups: constant light (LL) and control 12 h light/12 h dark photoperiod (LD). RNA isolated from E18 heart was subjected to microarray analysis (Affymetrix platform for 28,000 genes). Integrated transcriptional changes were assessed by gene ontology and pathway analysis. Significant differential expression was found for 383 transcripts in LL relative to LD fetal heart (280 up-regulated and 103 down-regulated); with 42 of them displaying a 1.5-fold or greater change in gene expression. Deregulated markers of cardiovascular disease accounted for alteration of diverse gene networks in LL fetal heart, including local steroidogenesis and vascular calcification, as well as cardiac hypertrophy, stenosis and necrosis/cell death. DNA integrity was also overrepresented, including a 2.1-fold increase of Hmga1 mRNA, which encodes for a profuse architectural transcription factor. microRNA analysis revealed up-regulation of miRNAs 218-1 and 501 and concurrent down-regulation of their validated target genes. In addition, persistent down-regulation of Kcnip2 mRNA and hypertrophy of the left ventricle were found in the heart from 90 days-old offspring from LL mothers. The dysregulation of a relevant fraction of the fetal cardiac transcriptome, together with the diversity and complexity of the gene networks altered by gestational chronodisruption, suggest enduring molecular changes which may shape the hypertrophy observed in the left ventricle of adult LL offspring. © 2013.

  1. Fetal Brain Behavior and Cognitive Development.

    ERIC Educational Resources Information Center

    Joseph, R.

    2000-01-01

    Presents information on prenatal brain development, detailing the functions controlled by the medulla, pons, and midbrain, and the implications for cognitive development. Concludes that fetal cognitive motor activity, including auditory discrimination, orienting, the wake-sleep cycle, fetal heart rate accelerations, and defensive reactions,…

  2. Fetal and neonatal thyrotoxicosis

    PubMed Central

    Batra, Chandar Mohan

    2013-01-01

    Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

  3. An effective strategy for decontamination, ex vivo expansion, and storage of human fetal liver hematopoietic stem cells.

    PubMed

    Rice, H E; Skarsgard, E D; Emani, V R; Zanjani, E D; Harrison, M R; Flake, A W

    1994-12-01

    The transplantation of human fetal tissue has the potential to cure a variety of life-threatening diseases. The strategy for procurement, quality control, and functional assessment of human fetal liver HSC may prove useful for the transplantation of other fetal tissues. In addition to technical limitations, there are ethical and legal issues which need to be resolved before widespread use of fetal tissue. Further development of regulatory standards for the acquisition and distribution of fetal tissues will foster the application of this novel technology.

  4. Retrospective study of the effect of remifentanil use during labor on fetal heart rate patterns.

    PubMed

    Boterenbrood, Danne; Wassen, Martine M; Visser, Gerard H A; Nijhuis, Jan G

    2018-01-01

    To investigate possible associations between remifentanil and the appearance of sinusoidal heart rate patterns in fetuses, and neonatal outcomes. The present retrospective cohort study included data from patients at over 37 weeks of singleton or multiple pregnancies attending Zuyderland Medical Center, Sittard, the Netherlands, in labor between June 1, and August 31, 2015. Patient data were stratified by whether remifentanil was administered during delivery (remifentanil group) or not (control group), and fetal heart rate tracings were reviewed to identify sinusoidal heart rate patterns. The neonatal outcomes compared were 5-minute Apgar scores and umbilical artery pH. There were 119 patients included in the study; 60 in the remifentanil group and 59 in the control group. Tracings from 20 (33%) patients in the remifentanil group exhibited a sinusoidal heart rate pattern after remifentanil administration, compared with 5 (8%) patients in the control group (P=0.001). The median time before the onset of sinusoidal patterns after remifentanil administration was 12 minutes. No adverse neonatal outcomes were recorded in either group. Remifentanil use during labor was associated with the occurrence of sinusoidal heart rate patterns in the fetus; this was not associated with adverse neonatal outcomes. © 2017 International Federation of Gynecology and Obstetrics.

  5. Stereological study of developing glomerular forms during human fetal kidney development.

    PubMed

    Dakovic Bjelakovic, Marija; Vlajkovic, Slobodan; Petrovic, Aleksandar; Bjelakovic, Marko; Antic, Milorad

    2018-05-01

    Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.

  6. Murine fetal echocardiography.

    PubMed

    Kim, Gene H

    2013-02-15

    Transgenic mice displaying abnormalities in cardiac development and function represent a powerful tool for the understanding the molecular mechanisms underlying both normal cardiovascular function and the pathophysiological basis of human cardiovascular disease. Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development. In order to study the role of genetic or pharmacologic alterations in the early development of cardiac function, ultrasound imaging of the live fetus has become an important tool for early recognition of abnormalities and longitudinal follow-up. Noninvasive ultrasound imaging is an ideal method for detecting and studying congenital malformations and the impact on cardiac function prior to death. It allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Until recently, imaging of fetal mouse hearts frequently involved invasive methods. The fetus had to be sacrificed to perform magnetic resonance microscopy and electron microscopy or surgically delivered for transillumination microscopy. An application of high-frequency probes with conventional 2-D and pulsed-wave Doppler imaging has been shown to provide measurements of cardiac contraction and heart rates during embryonic development with databases of normal developmental changes now available. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. High-frequency ultrasound imaging of the fetus has improved 2-D resolution and can provide excellent information on the early development of cardiac structures.

  7. Long term effects of fetal undernutrition on rat heart. Role of hypertension and oxidative stress

    PubMed Central

    Rodríguez-Rodríguez, Pilar; López de Pablo, Angel L.; García-Prieto, Concha F.; Somoza, Beatriz; Quintana-Villamandos, Begoña; Gómez de Diego, José J.; Gutierrez-Arzapalo, Perla Y.; Ramiro-Cortijo, David; González, M. Carmen

    2017-01-01

    Background and aims Fetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress. Methods Male and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography). Results At the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls. Conclusions 1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative

  8. The "Fetal Reserve Index": Re-Engineering the Interpretation and Responses to Fetal Heart Rate Patterns.

    PubMed

    Eden, Robert D; Evans, Mark I; Evans, Shara M; Schifrin, Barry S

    2018-01-01

    Electronic fetal monitoring (EFM) correlates poorly with neonatal outcome. We present a new metric: the "Fetal Reserve Index" (FRI), formally incorporating EFM with maternal, obstetrical, fetal risk factors, and excessive uterine activity for assessment of risk for cerebral palsy (CP). We performed a retrospective, case-control series of 50 term CP cases with apparent intrapartum neurological injury and 200 controls. All were deemed neurologically normal on admission. We compared the FRI against ACOG Category (I-III) system and long-term outcome parameters against ACOG monograph (NEACP) requirements for labor-induced fetal neurological injury. Abnormal FRI's identified 100% of CP cases and did so hours before injury. ACOG Category III identified only 44% and much later. Retrospective ACOG monograph criteria were found in at most 30% of intrapartum-acquired CP patients; only 27% had umbilical or neonatal pH <7.0. In this initial, retrospective trial, an abnormal FRI identified all cases of labor-related neurological injury more reliably and earlier than Category III, which may allow fetal therapy by intrauterine resuscitation. The combination of traditional EFM with maternal, obstetrical, and fetal risk factors creating the FRI performed much better as a screening test than EFM alone. Our quantified screening system needs further evaluation in prospective trials. © 2017 S. Karger AG, Basel.

  9. Human fetal bone cells in delivery systems for bone engineering.

    PubMed

    Tenorio, Diene M H; Scaletta, Corinne; Jaccoud, Sandra; Hirt-Burri, Nathalie; Pioletti, Dominique P; Jaques, Bertrand; Applegate, Lee Ann

    2011-11-01

    The aim of this study was to culture human fetal bone cells (dedicated cell banks of fetal bone derived from 14 week gestation femurs) within both hyaluronic acid gel and collagen foam, to compare the biocompatibility of both matrices as potential delivery systems for bone engineering and particularly for oral application. Fetal bone cell banks were prepared from one organ donation and cells were cultured for up to 4 weeks within hyaluronic acid (Mesolis®) and collagen foams (TissueFleece®). Cell survival and differentiation were assessed by cell proliferation assays and histology of frozen sections stained with Giemsa, von Kossa and ALP at 1, 2 and 4 weeks of culture. Within both materials, fetal bone cells could proliferate in three-dimensional structure at ∼70% capacity compared to monolayer culture. In addition, these cells were positive for ALP and von Kossa staining, indicating cellular differentiation and matrix production. Collagen foam provides a better structure for fetal bone cell delivery if cavity filling is necessary and hydrogels would permit an injectable technique for difficult to treat areas. In all, there was high biocompatibility, cellular differentiation and matrix deposition seen in both matrices by fetal bone cells, allowing for easy cell delivery for bone stimulation in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

  10. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muczynski, V.; CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses; INSERM, Unité 967, F-92265, Fontenay aux Roses

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation andmore » cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.« less

  11. Predicting the Future: Delivery Room Planning of Congenital Heart Disease Diagnosed by Fetal Echocardiography.

    PubMed

    Donofrio, Mary T

    2018-05-01

    Advances in prenatal imaging have improved the examination of the fetal cardiovascular system. Fetal echocardiography facilitates the prenatal diagnosis of congenital heart disease (CHD) and through sequential examination, allows assessment of fetal cardiac hemodynamics, predicting the evolution of anatomical and functional cardiovascular abnormalities in utero and during the transition to a postnatal circulation at delivery. This approach allows detailed diagnosis with prenatal counseling and enables planning to define perinatal management, selecting the fetuses at a risk of postnatal hemodynamic instability who are likely to require a specialized delivery plan. The prenatal diagnosis and management of critical neonatal CHD has been shown to play an important role in improving the outcome of newborns with these conditions, allowing timely stabilization of the circulation prior to cardiac intervention or surgery, thus reducing the risk of perioperative morbidity and mortality. Diagnostic protocols aimed at risk-stratifying severity and potential postnatal compromise in fetuses with CHD have been developed to identify those who may require special intervention at birth or within the first days of life. In addition, new methodologies are being studied to improve the accuracy of prediction of disease severity. Perinatal management of neonates with a prenatal diagnosis of CHD requires a close collaboration between obstetric, neonatal, and cardiology services. In this article, the management of fetuses with CHD will be discussed, along with summarizing the in utero and fetal echocardiographic findings used for risk stratification of newborns with CHD and reviewing the basic principles used for planning for neonatal resuscitation and initial transitional care of these complex newborns. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Ethnic analogies and differences in fetal heart rate variability signal: A retrospective study.

    PubMed

    Tagliaferri, Salvatore; Esposito, Francesca Giovanna; Fagioli, Rosa; Di Cresce, Marco; Sacchi, Lucia; Signorini, Maria Gabriella; Campanile, Marta; Martinelli, Pasquale; Magenes, Giovanni

    2017-02-01

    We aimed to analyze computerized cardiotocographic (cCTG) parameters (including fetal heart rate baseline, short-term variability, Delta, long-term irregularity [LTI], interval index [II], low frequency [LF], movement frequency [MF], high frequency [HF], and approximate entropy [ApEn]) in physiological term pregnancies in order to correlate them with ethnic differences. The clinical meaning of numerical parameters may explain physiological or paraphysiological phenomena that occur in fetuses of different ethnic origins. A total of 696 pregnant women, including 384 from Europe, 246 from sub-Saharan Africa, 45 from South-East Asia, and 21 from South America, were monitored from the 37th to the 41st week of gestation. Statistical analysis was performed with the analysis of variance test, Pearson correlation test and receiver-operator curves (P < 0.05). Our results showed statistically significant differences (P < 0.05) between white and black women for Delta, LTI, LF, MF, HF, and ApEn; between white and Asian women for Delta, LTI, MF, and the LF/(HF + MF) ratio; and between white and Latina women for Delta, LTI, and ApEn. In particular, Delta and LTI performed better in the white group than in the black, Asian, and Latina groups. Instead, LF, MF, HF, and ApEn performed better in the black than in the white group. Our results confirmed the integrity and normal functionality of both central and autonomic nervous system components for all fetuses investigated. Therefore, CTG monitoring should include both linear and nonlinear components of fetal heart rate variability in order to avoid misinterpretations of the CTG trace among ethnic groups. © 2016 Japan Society of Obstetrics and Gynecology.

  13. Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans.

    PubMed

    Wiputra, Hadi; Lai, Chang Quan; Lim, Guat Ling; Heng, Joel Jia Wei; Guo, Lan; Soomar, Sanah Merchant; Leo, Hwa Liang; Biwas, Arijit; Mattar, Citra Nurfarah Zaini; Yap, Choon Hwai

    2016-12-01

    There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ∼25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts. Copyright © 2016 the American Physiological Society.

  14. [Fetal heart rate patterns of breech presentations during expulsion. A comparative study with cephalic presentations].

    PubMed

    Bourtembourg, A; Ramanah, R; Martin, A; Pugin-Vivot, A; Maillet, R; Riethmuller, D

    2015-06-01

    Expulsion upon vaginal delivery is a period at risk for the foetus, especially in case of breech presentation. In fact, monitoring the fetal well-being is complex in this phase. The correct interpretation of fetal heart rate (FHR) during expulsion, using Melchior's classification, is important because it helps screen for fetal acidosis. The aim of this study was to determine if it was possible to tolerate an abnormal FHR during expulsion of breech presentations. A retrospective study was conducted to compare FHR during expulsion and neonatal results between breech and cephalic presentations at Besançon's university hospital. We collected data from 118 breech presentations and 236 cephalic presentations. Melchior's FHR classification types were significantly different between breech and cephalic presentations with a majority of type 1. Neonatal results were significantly less favorable for breech presentations, but without any increase in mortality and in severe morbidity. Melchior's expulsion FHR classification seems to be applicable for breech presentations with a different distribution of FHR types compared to cephalic presentations. Following the results of this study, it seems to be possible to tolerate an abnormal FHR during expulsion of breech presentation, so far as is reasonable. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Non-invasive Fetal ECG Signal Quality Assessment for Multichannel Heart Rate Estimation.

    PubMed

    Andreotti, Fernando; Graser, Felix; Malberg, Hagen; Zaunseder, Sebastian

    2017-12-01

    The noninvasive fetal ECG (NI-FECG) from abdominal recordings offers novel prospects for prenatal monitoring. However, NI-FECG signals are corrupted by various nonstationary noise sources, making the processing of abdominal recordings a challenging task. In this paper, we present an online approach that dynamically assess the quality of NI-FECG to improve fetal heart rate (FHR) estimation. Using a naive Bayes classifier, state-of-the-art and novel signal quality indices (SQIs), and an existing adaptive Kalman filter, FHR estimation was improved. For the purpose of training and validating the proposed methods, a large annotated private clinical dataset was used. The suggested classification scheme demonstrated an accuracy of Krippendorff's alpha in determining the overall quality of NI-FECG signals. The proposed Kalman filter outperformed alternative methods for FHR estimation achieving accuracy. The proposed algorithm was able to reliably reflect changes of signal quality and can be used in improving FHR estimation. NI-ECG signal quality estimation and multichannel information fusion are largely unexplored topics. Based on previous works, multichannel FHR estimation is a field that could strongly benefit from such methods. The developed SQI algorithms as well as resulting classifier were made available under a GNU GPL open-source license and contributed to the FECGSYN toolbox.

  16. Electronic fetal monitoring: family medicine obstetrics.

    PubMed

    Rodney, John R M; Huntley, Benjamin J F; Rodney, Wm Macmillan

    2012-03-01

    Electronic fetal monitoring assesses fetal health during the prenatal and intrapartum process. Intermittent auscultation does not detect key elements of fetal risk, such as beat-to-beat variability. Family medicine obstetric fellowships have contributed new knowledge to this process by articulating a method of analysis that builds on evidence-based recommendations from the American College of Obstetrics and Gynecology as well as the National Institute of Child Health and Development. This article summarizes the development, interpretation, and management of electronic fetal heart rate patterns and tracings. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. [Significance of amnioinfusion and amniotic fluid exchange under continuous internal fetal heart rate monitoring for management of fetal distress during labor].

    PubMed

    Zhao, S; Ai, L; Zhang, H

    2000-01-01

    To discuss the significance of amnioinfusion and amniotic fluid exchange under continuous internal fetal heart rate (FHR) monitoring for management of fetal distress during labor. 136 cases with frequent variable deceleration (VD) and meconium stained amniotic fluid during labor were divided into two groups: the study group (68 cases) and the control group (68 cases). The former were treated by amnioinfusion and amniotic fluid exchange, while oxygen inhalation, change of body position, and intravenous infusion for the control group. In the study group, VD disappeared or relieved in 62 cases obviously, and the efficacy rate reached 91.2% (62/68). 48 cases with II degree meconium stained amniotic fluid were treated by amniotic fluid exchange, amniotic fluid became clear or turned to I degree stained in 39 cases. In the control group, VD relieved in 20 cases, the efficacy rate was 19.4%, significantly lower than that of the study group (P < 0.01). In the study group, cesarean section rate was 14.7% neonatal asphyxia 7.4% while they were 47.1% and 48.5% in the control group respectively (P < 0.01; P < 0.01). Neonatal pneumonia caused by meconium aspiration occurred in 13 cases, meconium aspiration syndrome (MAS) 8 cases, with 5 newborns died in the control group, while there was no neonatal death in the study group. There was no significant difference on puerperal morbidity between the 2 groups (P > 0.05). Amnioinfusion and AF exchange during labor are one of the effective treatment methods for fetal distress and prevention for MAS.

  18. Maternal predictive factors for fetal congenital heart block in pregnant mothers positive for anti-SS-A antibodies.

    PubMed

    Tsuboi, Hiroto; Sumida, Takayuki; Noma, Hisashi; Yamagishi, Kazumasa; Anami, Ai; Fukushima, Kotaro; Horigome, Hitoshi; Maeno, Yasuki; Kishimoto, Mitsumasa; Takasaki, Yoshinari; Nakayama, Masahiro; Waguri, Masako; Sago, Haruhiko; Murashima, Atsuko

    2016-07-01

    To determine the maternal predictive factors for fetal congenital heart block (CHB) in pregnancy in mothers positive for anti-SS-A antibodies. The Research Team for Surveillance of Autoantibody-Exposed Fetuses and Treatment of Neonatal Lupus Erythematosus, the Research Program of the Japan Ministry of Health, Labor and Welfare, performed a national survey on pregnancy of mothers positive for anti-SS-A antibodies. We analyzed 635 pregnant mothers who tested positive for anti-SS-A antibodies before conception but had no previous history of fetal CHB. We performed univariate and multivariate analysis (models 1, 2, and 3 using different set of independent variables) investigated the relation between risk of fetal CHB and maternal clinical features. Of the 635 pregnant mothers, fetal CHB was detected in 16. Univariate analysis showed that fetal CHB associated with use of corticosteroids before conception (OR 3.72, p = 0.04), and negatively with use of corticosteroids (equivalent doses of prednisolone (PSL), at ≥10 mg/day) after conception before 16-week gestation (OR 0.17, p = 0.03). In multivariate analysis, model 1 identified the use of corticosteroids before conception (OR 4.28, p = 0.04) and high titer of anti-SS-A antibodies (OR 3.58, p = 0.02) as independent and significant risk factors, and model 3 identified use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as independent protective factor against the development of fetal CHB (OR 0.16, p = 0.03). Other maternal clinical features did not influence the development of fetal CHB. The results identified high titers of anti-SS-A antibodies and use of corticosteroids before conception as independent risk factors, and use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as an independent protective factor for fetal CHB.

  19. Ibuprofen results in alterations of human fetal testis development

    PubMed Central

    Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

    2017-01-01

    Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

  20. Origin of bombesin-like peptides in human fetal lung.

    PubMed

    Yoshizaki, K; de Bock, V; Solomon, S

    1984-02-27

    Four different forms of bombesin-like immunoreactive peaks were detected in extracts of human fetal lung by the use of reversed-phase high performance liquid chromatography (HPLC). Peaks I, II, III and IV, (increasing retention time), were eluted using a 14-38% of acetonitrile gradient containing 0.1% trifluoroacetic acid (TFA). Peak II was the major material found in the extract of human fetal lung obtained at 16-20 weeks gestation. None of the four compounds contained in the eluted peaks had the same retention time as amphibian bombesin or porcine gastrin releasing peptide (GRP). On reversed-phase HPLC using two different solvent systems TFA or heptafluorobutyric acid (HFBA) as a hydrophobic counter ion, and in gel filtration chromatography, the chromatographic behavior of the main peak (peak II) was the same as that of the carboxyl terminal fragments of GRP, GRP18-27 or GRP19-27. This suggested that the peptide(s) in peak II resembled in composition the carboxy terminal 9 or 10 amino acids of porcine GRP. Following tryptic digestion the material in peak IV was converted to the more polar compound present in peak II. Two other peptide peaks were eluted close to peak II and these were presumed to be a modification of this main peak. One of the possible biosynthetic steps in the formation of bombesin-like peptides in human fetal lung could be a tryptic conversion of a less polar peptide to a more polar form (peak IV to II).

  1. [Analysis of an ophthalmic pathology cohort of human fetal eyes with regard to interesting findings].

    PubMed

    Herwig, M C; Müller, A M; Holz, F G; Loeffler, K U

    2010-11-01

    Information on the evaluation of prenatal ocular findings is sparse. This article provides an overview of the morphology in a cohort of human fetal eyes, with particular emphasis on interesting findings. The study investigated 216 eyes from 115 human fetuses. The majority of fetal eyes presented with a regular phenotype. Rarely, unexpected findings were discovered in fetuses with or without systemic malformations. Routine evaluation of fetal eyes reveals-albeit rarely-new aspects providing further knowledge and occasionally enabling the exact classification of syndromes.

  2. Insights in spatio-temporal characterization of human fetal neural stem cells.

    PubMed

    Martín-Ibáñez, Raquel; Guardia, Inés; Pardo, Mónica; Herranz, Cristina; Zietlow, Rike; Vinh, Ngoc-Nga; Rosser, Anne; Canals, Josep M

    2017-05-01

    Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum. We observed that, as fetal brain development proceeds, the number of neural precursors is diminished and post-mitotic cells are increased. In turn, primary cells obtained from older embryos are more sensitive to the dissociation process, their viability is diminished and they present lower proliferation ratios compared to younger embryos. However, independently of the developmental stage of derivation proliferation ratios were very low in all cases. Improvements in the expansion rates were achieved by mechanical, instead of enzymatic, dissociation of neurospheres but not by changes in the seeding densities. Regardless of the developmental stage, neurosphere cultures presented large variability in the viability and proliferation rates during the initial 3-4 passages, but stabilized achieving significant expansion rates at passage 5 to 6. This was true also for all brain regions except cerebellar derived cultures that did not expand. Interestingly, the brain region of hfNSC derivation influences the expansion potential, being forebrain, cortex and WGE derived cells the most expandable compared to cerebellar. Short term expansion partially compromised the regional identity of cortical but not WGE cultures. Nevertheless, both expanded cultures were

  3. Automatic evaluation of intrapartum fetal heart rate recordings: a comprehensive analysis of useful features.

    PubMed

    Chudáček, V; Spilka, J; Janků, P; Koucký, M; Lhotská, L; Huptych, M

    2011-08-01

    Cardiotocography is the monitoring of fetal heart rate (FHR) and uterine contractions (TOCO), used routinely since the 1960s by obstetricians to detect fetal hypoxia. The evaluation of the FHR in clinical settings is based on an evaluation of macroscopic morphological features and so far has managed to avoid adopting any achievements from the HRV research field. In this work, most of the features utilized for FHR characterization, including FIGO, HRV, nonlinear, wavelet, and time and frequency domain features, are investigated and assessed based on their statistical significance in the task of distinguishing the FHR into three FIGO classes. We assess the features on a large data set (552 records) and unlike in other published papers we use three-class expert evaluation of the records instead of the pH values. We conclude the paper by presenting the best uncorrelated features and their individual rank of importance according to the meta-analysis of three different ranking methods. The number of accelerations and decelerations, interval index, as well as Lempel-Ziv complexity and Higuchi's fractal dimension are among the top five features.

  4. Fetal distress and the condition of newborn infants.

    PubMed Central

    Sykes, G S; Molloy, P M; Johnson, P; Stirrat, G M; Turnbull, A C

    1983-01-01

    In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth. PMID:6412897

  5. A modified fetal heart rate tracing interpretation system for prediction of cesarean section

    PubMed Central

    Schnettler, William T.; Rogers, Jennifer; Barber, Rachel E.; Hacker, Michele R.

    2013-01-01

    Objective To investigate whether a modified version of the 2008 National Institute of Child Health and Human Development (NICHD) interpretation system upon admission decreases cesarean delivery risk. Methods This retrospective cohort study ascribed a modified category to the first 30 min of fetal heart rate (FHR) tracings in labor. Category I was divided into two subsets (Ia and Ib) by the presence of accelerations. Category II was divided into four subsets (IIa–IId) based on baseline FHR, variability, response to stimulation and decelerations. Log-binomial regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). Results A category was ascribed to 910 women. Most FHR tracings were Category Ia (65.8%), Ib (7.7%), IIb (11.8%) and IId (14.0%). Category Ib tracings (fewer than two accelerations) were 2.26 (95% CI: 1.13–4.52) times more likely to result in cesarean delivery for abnormal FHR tracing than Category Ia tracings. A similar increase in risk was seen when comparing Category IIb and Category IId with Category Ia. Conclusion Application of a modified version of the 2008 NICHD FHR interpretation system to the initial 30 min of labor can identify women at increased risk of cesarean delivery for abnormal FHR tracing. PMID:21942513

  6. Morphologic analysis of artifacts in human fetal eyes confounding histopathologic investigations.

    PubMed

    Herwig, Martina C; Müller, Annette M; Holz, Frank G; Loeffler, Karin U

    2011-04-25

    Human fetal eyes are an excellent source for studies of the normal ocular development and for examining early ocular changes associated with various syndromes in the context of a pediatric pathologic or prenatal sonographic diagnosis. However, artifacts caused by different factors often render an exact interpretation difficult. In this study, the frequency and extent of artifacts in human fetal eyes were investigated with the aim of distinguishing more precisely these artifacts from real findings, allowing also for a more diligent forensic interpretation. The cohort included 341 fetal eyes, ranging in age from 8 to 38 weeks of gestation, that were investigated macroscopically and by light microscopy. In most specimens, artifacts such as pigment spillage and autolytic changes of the retina were noted. Nearly all specimens showed changes of the lens with remarkable similarities to cataractous lenses in adult eyes. Structural ocular changes associated with systemic syndromes were also observed and in most instances could be distinguished from artifacts. Morphologic changes in fetal eyes should be classified in artifacts caused by way of abortion, mechanical effects from the removal of the eyes, delayed fixation with autolysis, and the fixative itself and should be distinguished from genuine structural abnormalities associated with ocular or systemic disease. This classification can be fairly difficult and requires experience. In addition, lens artifacts are often misleading, and the diagnosis of a fetal cataract should not be made based on histopathologic examination alone.

  7. Fetal phonocardiography--past and future possibilities.

    PubMed

    Kovács, Ferenc; Horváth, Csaba; Balogh, Adám T; Hosszú, Gábor

    2011-10-01

    The paper presents an overview of the 15 year long development of fetal phonocardiography including the works on the applied signal processing methods for identification of sound components. Based on the improvements achieved on this field, the paper shows that beyond the traditional CTG test the phonocardiography may be successfully applied for long-term fetal measurements and home monitoring. In addition, by indication of heart murmurs based on a comprehensive analysis of the recorded heart sound congenital heart defects can also be detected together with additional features in the third trimester. This makes an early widespread screening possible combined with the prescribed CTG test even at home using a telemedicine system. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Fetal magnetocardiography measurements with an array of microfabricated optically pumped magnetometers

    NASA Astrophysics Data System (ADS)

    Alem, Orang; Sander, Tilmann H.; Mhaskar, Rahul; LeBlanc, John; Eswaran, Hari; Steinhoff, Uwe; Okada, Yoshio; Kitching, John; Trahms, Lutz; Knappe, Svenja

    2015-06-01

    Following the rapid progress in the development of optically pumped magnetometer (OPM) technology for the measurement of magnetic fields in the femtotesla range, a successful assembly of individual sensors into an array of nearly identical sensors is within reach. Here, 25 microfabricated OPMs with footprints of 1 cm3 were assembled into a conformal array. The individual sensors were inserted into three flexible belt-shaped holders and connected to their respective light sources and electronics, which reside outside a magnetically shielded room, through long optical and electrical cables. With this setup the fetal magnetocardiogram of a pregnant woman was measured by placing two sensor belts over her abdomen and one belt over her chest. The fetal magnetocardiogram recorded over the abdomen is usually dominated by contributions from the maternal magnetocardiogram, since the maternal heart generates a much stronger signal than the fetal heart. Therefore, signal processing methods have to be applied to obtain the pure fetal magnetocardiogram: orthogonal projection and independent component analysis. The resulting spatial distributions of fetal cardiac activity are in good agreement with each other. In a further exemplary step, the fetal heart rate was extracted from the fetal magnetocardiogram. Its variability suggests fetal activity. We conclude that microfabricated optically pumped magnetometers operating at room temperature are capable of complementing or in the future even replacing superconducting sensors for fetal magnetocardiography measurements.

  9. Maternal salivary testosterone in pregnancy and fetal neuromaturation.

    PubMed

    Voegtline, Kristin M; Costigan, Kathleen A; DiPietro, Janet A

    2017-11-01

    Testosterone exposure during pregnancy has been hypothesized as a mechanism for sex differences in brain and behavioral development observed in the postnatal period. The current study documents the natural history of maternal salivary testosterone from 18 weeks gestation of pregnancy to 6 months postpartum, and investigates associations with fetal heart rate, motor activity, and their integration. Findings indicate maternal salivary testosterone increases with advancing gestation though no differences by fetal sex were detected. High intra-individual stability in prenatal testosterone levels extend into the postnatal period, particularly for pregnancies with male fetuses. With respect to fetal development, by 36 weeks gestation higher maternal prenatal salivary testosterone was significantly associated with faster fetal heart rate and less optimal somatic-cardiac integration. Measurement of testosterone in saliva is a useful tool for repeated-measures studies of hormonal concomitants of pregnancy. Moreover, higher maternal testosterone levels are associated with modest interference to fetal neurobehavioral development. © 2017 Wiley Periodicals, Inc.

  10. Detection of a Heart Defect in the Fetus

    MedlinePlus

    ... problems : There is a wide range of acceptable fetal heart rates (normal is between 120 and 160 but many ... usually go away shortly after birth. More important fetal heart problems include tachycardia (hear rate too fast) and bradycardia (heart rate too slow). ...

  11. Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity.

    PubMed

    Maloyan, Alina; Muralimanoharan, Sribalasubashini; Huffman, Steven; Cox, Laura A; Nathanielsz, Peter W; Myatt, Leslie; Nijland, Mark J

    2013-10-01

    Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD.

  12. Physiological reactivity of pregnant women to evoked fetal startle

    PubMed Central

    DiPietro, Janet A.; Voegtline, Kristin M.; Costigan, Kathleen A.; Aguirre, Frank; Kivlighan, Katie; Chen, Ping

    2013-01-01

    Objective The bidirectional nature of mother-child interaction is widely acknowledged during infancy and childhood. Prevailing models during pregnancy focus on unidirectional influences exerted by the pregnant woman on the developing fetus. Prior work has indicated that the fetus also affects the pregnant woman. Our objective was to determine whether a maternal psychophysiological response to stimulation of the fetus could be isolated. Methods Using a longitudinal design, an airborne auditory stimulus was used to elicit a fetal heart rate and motor response at 24 (n = 47) and 36 weeks (n = 45) gestation. Women were blind to condition (stimulus versus sham). Maternal parameters included cardiac (heart rate) and electrodermal (skin conductance) responses. Multilevel modeling of repeated measures with 5 data points per second was used to examine fetal and maternal responses. Results As expected, compared to a sham condition, the stimulus generated a fetal motor response at both gestational ages, consistent with a mild fetal startle. Fetal stimulation was associated with significant, transient slowing of maternal heart rate coupled with increased skin conductance within 10 s of the stimulus at both gestational ages. Nulliparous women showed greater electrodermal responsiveness. The magnitude of the fetal motor response significantly corresponded to the maternal skin conductance response at 5, 10, 15, and 30 s following stimulation. Conclusion Elicited fetal movement exerts an independent influence on the maternal autonomic nervous system. This finding contributes to current models of the dyadic relationship during pregnancy between fetus and pregnant woman. PMID:24119937

  13. Amniocentesis for fetal lung maturity: will it become obsolete?

    PubMed

    Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

    2013-01-01

    AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

  14. Prototype of a wearable system for remote fetal monitoring during pregnancy.

    PubMed

    Fanelli, Andrea; Ferrario, Manuela; Piccini, Luca; Andreoni, Giuseppe; Matrone, Giulia; Magenes, Giovanni; Signorini, Maria G

    2010-01-01

    Fetal Heart Rate (FHR) monitoring gives important information about the fetus health state during pregnancy. This paper presents a new prototype for remote fetal monitoring. The device will allow to monitor FHR in a domiciliary context and to send fetal ECG traces to a hospital facility, where clinicians can interpret them. In this way the mother could receive prompt feedback about fetal wellbeing. The system is characterized by two units: (i) a wearable unit endowed with textile electrodes for abdominal ECG recordings and with a Field Programmable Gate Array (FPGA) board for fetal heart rate (FHR) extraction; (ii) a dock station for the transmission of the data through the telephone line. The system will allow to reduce costs in fetal monitoring, improving the assessment of fetal conditions. The device is actually in development state. In this paper, the most crucial aspects behind its fulfillment are discussed.

  15. A protocol to study ex vivo mouse working heart at human-like heart rate.

    PubMed

    Feng, Han-Zhong; Jin, Jian-Ping

    2018-01-01

    Genetically modified mice are widely used as experimental models to study human heart function and diseases. However, the fast rate of normal mouse heart at 400-600bpm limits its capacity of assessing kinetic parameters that are important for the physiology and pathophysiology of human heart that beats at a much slower rate (75-180bpm). To extend the value of mouse models, we established a protocol to study ex vivo mouse working hearts at a human-like heart rate. In the presence of 300μM lidocaine to lower pacemaker and conductive activities and prevent arrhythmia, a stable rate of 120-130bpm at 37°C is achieved for ex vivo mouse working hearts. The negative effects of decreased heart rate on force-frequency dependence and lidocaine as a myocardial depressant on intracellular calcium can be compensated by using a higher but still physiological level of calcium (2.75mM) in the perfusion media. Multiple parameters were studied to compare the function at the human-like heart rate with that of ex vivo mouse working hearts at the standard rate of 480bpm. The results showed that the conditions for slower heart rate in the presence of 300μM lidocaine did not have depressing effect on left ventricular pressure development, systolic and diastolic velocities and stroke volume with maintained positive inotropic and lusitropic responses to β-adrenergic stimulation. Compared with that at 480bpm, the human-like heart rate increased ventricular filling and end diastolic volume with enhanced Frank-Starling responses. Coronary perfusion was increased from longer relaxation time and interval between beats whereas cardiac efficiency was significantly improved. Although the intrinsic differences between mouse and human heart remain, this methodology for ex vivo mouse hearts to work at human-like heart rate extends the value of using genetically modified mouse models to study cardiac function and human heart diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Recent advances in fetal near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    D'Antona, Donato; Aldrich, Clive J.; O'Brien, Patrick; Lawrence, Sally; Delpy, David T.; Wyatt, John S.

    1997-01-01

    Fetal brain injury resulting from hypoxia and ischemia during labor remains an important cause of death and long- term disability. However, little is known about fetal brain oxygenation and hemodynamics. There are currently no satisfactory clinical techniques for fetal monitoring and there remains a need for a new method to assess brain oxygenation. Fetal near infrared spectroscopy (NIRS) is a new technique that allows noninvasive observation of changes in the cerebral concentrations of oxyhemoglobin and deoxyhemoglobin to be made during labor. A specially designed optical probe is inserted through the dilated cervix and placed against the fetal head. It is then possible to compare changes in NIRS data with other observations of fetal conditions, such as fetal heart rate and acid-base status.

  17. The influence of physical activity during pregnancy on maternal, fetal or infant heart rate variability: a systematic review.

    PubMed

    Dietz, Pavel; Watson, Estelle D; Sattler, Matteo C; Ruf, Wolfgang; Titze, Sylvia; van Poppel, Mireille

    2016-10-26

    Physical activity (PA) during pregnancy has been shown to be associated with several positive effects for mother, fetus, and offspring. Heart rate variability (HRV) is a noninvasive and surrogate marker to determine fetal overall health and the development of fetal autonomic nervous system. In addition, it has been shown to be significantly influenced by maternal behavior. However, the influence of maternal PA on HRV has not yet been systematically reviewed. Therefore, the aim of this systematic review was to assess the influence of regular maternal PA on maternal, fetal or infant HRV. A systematic literature search following a priori formulated criteria of studies that examined the influence of regular maternal PA (assessed for a minimum period of 6 weeks) on maternal, fetal or infant HRV was performed in the databases Pubmed and SPORTDiscus. Quality of each study was assessed using the standardized Quality Assessment Tool for Quantitative Studies (QATQS). Nine articles were included into the present systematic review: two intervention studies, one prospective longitudinal study, and six post-hoc analysis of subsets of the longitudinal study. Of these articles four referred to maternal HRV, five to fetal HRV, and one to infant HRV. The overall global rating for the standardized quality assessment of the articles was moderate to weak. The articles regarding the influence of maternal PA on maternal HRV indicated contrary results. Five of five articles regarding the influence of maternal PA on fetal HRV showed increases of fetal HRV on most parameters depending on maternal PA. The article referring to infant HRV (measured one month postnatal) showed an increased HRV. Based on the current evidence available, our overall conclusion is that the hypothesis that maternal PA influences maternal HRV cannot be supported, but there is a trend that maternal PA might increase fetal and infant HRV (clinical conclusion). Therefore, we recommend that further, high quality studies

  18. n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

    PubMed

    Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

    2015-09-01

    This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. In utero exposure to venlafaxine, a serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat.

    PubMed

    Laurent, Laetitia; Huang, Chunwei; Ernest, Sheila R; Berard, Anick; Vaillancourt, Cathy; Hales, Barbara F

    2016-12-01

    Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT 2B /Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044-1055, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Amniocentesis for Fetal Lung Maturity: Will It Become Obsolete?

    PubMed Central

    Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

    2013-01-01

    Amniocentesis for fetal lung maturity has historically been performed for many reasons: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate. PMID:24826202

  1. Fetal heart rate abnormalities during and after external cephalic version: Which fetuses are at risk and how are they delivered?

    PubMed

    Kuppens, Simone M; Smailbegovic, Ida; Houterman, Saskia; de Leeuw, Ingrid; Hasaart, Tom H

    2017-10-17

    Fetal heart rate abnormalities (FHR) during and after external cephalic version (ECV) are relatively frequent. They may raise concern about fetal wellbeing. Only occasionally they may lead to an emergency cesarean section. Prospective cohort study in 980 women (> 34 weeks gestation) with a singleton fetus in breech presentation. During and after external cephalic version (ECV) FHR abnormalities were recorded. Obstetric variables and delivery outcome were evaluated. Primary outcome was to identify which fetuses are at risk for FHR abnormalities. Secondary outcome was to identify a possible relationship between FHR abnormalities during and after ECV and mode of delivery and fetal distress during subsequent labor. The overall success rate of ECV was 60% and in 9% of the attempts there was an abnormal FHR pattern. In two cases FHR abnormalities after ECV led to an emergency CS. Estimated fetal weight per 100 g (OR 0.90, CI: 0.87-0.94) and longer duration of the ECV-procedure (OR 1.13, CI: 1.05-1.21) were factors significantly associated with the occurrence of FHR abnormalities. FHR abnormalities were not associated with the mode of delivery or the occurrence of fetal distress during subsequent labor. FHR abnormalities during and after ECV are more frequent with lower estimated fetal weight and longer duration of the procedure. FHR abnormalities during and after ECV have no consequences for subsequent mode of delivery. They do not predict whether fetal distress will occur during labor. The Eindhoven Breech Intervention Study, NCT00516555 . Date of registration: August 13, 2007.

  2. A vector fetal magnetocardiogram system with high sensitivity

    NASA Astrophysics Data System (ADS)

    Kandori, Akihiko; Miyashita, Tsuyoshi; Tsukada, Keiji; Horigome, Hitoshi; Asaka, Mitsuhiro; Shigemitsu, Sadahiko; Takahashi, Miho; Terada, Yasushi; Mitsui, Toshio; Chiba, Yoshihide

    1999-12-01

    The vector fetal magnetocardiogram (V-FMCG) system that measures the three orthogonal components of the magnetic field from a fetal heart has been developed to clearly observe fetal cardiac activity during pregnancy by using the superconducting quantum interference device. To detect a clear V-FMCG signal, the bottom of the cryostat was made of thin glass-fiber-reinforced plastic and the total length between the pickup coil to the outer surface is 12 mm. Because the cryostat bottom was made thinner, the area of the cryostat's top and bottom could be made smaller, thus a low evaporation loss (<1.2 l per day) and a long refilling interval (>10 days) were obtained. The gantry was able to tilt the cryostat and the bed could move in three axis directions, which made it possible to easily locate the vector pickup coil at an optimum position to obtain the maximum magnetic field from a fetal heart. We obtained V-FMCGs from 21 normal fetuses with gestation periods of 27-38 weeks. Using these vector signals, the dipoles were estimated and the relationship between the strength of the dipole moments and the number of gestation weeks could be obtained. Thus, V-FMCG seems to represent a new noninvasive tool for clearly detecting the electrophysiological activity of a fetal heart.

  3. Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.

    PubMed

    Szabo, Linda; Morey, Robert; Palpant, Nathan J; Wang, Peter L; Afari, Nastaran; Jiang, Chuan; Parast, Mana M; Murry, Charles E; Laurent, Louise C; Salzman, Julia

    2015-06-16

    The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.

  4. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.

    PubMed

    Wang, Kimberley C W; Zhang, Lei; McMillen, I Caroline; Botting, Kimberley J; Duffield, Jaime A; Zhang, Song; Suter, Catherine M; Brooks, Doug A; Morrison, Janna L

    2011-10-01

    Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

  5. Fetal Cerebrovascular Resistance and Neonatal EEG Predict 18-month Neurodevelopmental Outcome in Infants with Congenital Heart Disease

    PubMed Central

    Williams, Ismee A.; Tarullo, Amanda R.; Grieve, Philip G.; Wilpers, Abigail; Vignola, Emilia F.; Myers, Michael M.; Fifer, William P.

    2012-01-01

    Objectives The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in congenital heart disease (CHD) survivors. Methods Fetuses < 24 wks gestational age (GA) were enrolled in this prospective pilot study for serial Doppler assessment of the middle cerebral and umbilical artery. The cerebral-to-placental resistance ratio (CPR) and MCA pulsatility index (PI) z-scores for GA were calculated. After birth, subjects underwent high-density (128-lead) electroencephalogram (EEG) and beta frequency (12–24Hz) band EEG power, a measure of local neural synchrony, was analyzed. Neurodevelopment was assessed at 18-months with the Bayley Scales of Infant Development III (BSID). Results 13 subjects were enrolled: 4 with hypoplastic left heart syndrome (HLHS), 4 with transposition of the great arteries (TGA), and 5 with tetralogy of Fallot (TOF). Compared with subjects with normal CPR, those with CPR<1(N=7) had lower mean BSID cognitive scores (91.4±4.8 vs. 99.2±3.8, p=.008). Fetal MCA PI z-score also correlated with BSID cognitive score (r=.589, p=0.044) as did neonatal EEG left frontal polar (r=.58, p=.037) and left frontal (r=.77,p=.002) beta power. Furthermore, fetal Doppler measures were associated with EEG power: fetuses with CPR<1 had lower left frontal polar (t=2.36, p=.038) and left frontal (t=2.85, p=.016) beta power as newborns compared with fetuses with normal CPR, and fetal MCA PI z-score correlated with neonatal EEG left frontal polar (r=.596, p=.04) and left frontal (r=.598, p=.04) beta power. Conclusions In CHD fetuses with HLHS, TGA, and TOF, abnormal cerebrovascular resistance predicted decreased neonatal EEG left frontal beta power and lower 18-mo cognitive development scores. PMID:22351034

  6. Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

    PubMed

    Turan, Sifa; Aberdeen, Graham W; Thompson, Loren P

    2017-10-01

    Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( n = 7) or hypoxia (10.5% O 2 , n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( n = 21) and hypoxic ( n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure. Copyright © 2017 the American Physiological

  7. Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

    PubMed Central

    Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

    2015-01-01

    Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

  8. Increased reprogramming of human fetal hepatocytes compared with adult hepatocytes in feeder-free conditions.

    PubMed

    Hansel, Marc C; Gramignoli, Roberto; Blake, William; Davila, Julio; Skvorak, Kristen; Dorko, Kenneth; Tahan, Veysel; Lee, Brian R; Tafaleng, Edgar; Guzman-Lepe, Jorge; Soto-Gutierrez, Alejandro; Fox, Ira J; Strom, Stephen C

    2014-01-01

    Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be a useful source of hepatocytes for basic research and transplantation if efficient and effective differentiation protocols were developed and problems with tumorigenicity could be overcome. Recent evidence suggests that the cell of origin may affect hiPSC differentiation. Thus, hiPSCs generated from hepatocytes may differentiate back to hepatocytes more efficiently than hiPSCs from other cell types. We examined the efficiency of reprogramming adult and fetal human hepatocytes. The present studies report the generation of 40 hiPSC lines from primary human hepatocytes under feeder-free conditions. Of these, 37 hiPSC lines were generated from fetal hepatocytes, 2 hiPSC lines from normal hepatocytes, and 1 hiPSC line from hepatocytes of a patient with Crigler-Najjar syndrome, type 1. All lines were confirmed reprogrammed and expressed markers of pluripotency by gene expression, flow cytometry, immunocytochemistry, and teratoma formation. Fetal hepatocytes were reprogrammed at a frequency over 50-fold higher than adult hepatocytes. Adult hepatocytes were only reprogrammed with six factors, while fetal hepatocytes could be reprogrammed with three (OCT4, SOX2, NANOG) or four factors (OCT4, SOX2, NANOG, LIN28 or OCT4, SOX2, KLF4, C-MYC). The increased reprogramming efficiency of fetal cells was not due to increased transduction efficiency or vector toxicity. These studies confirm that hiPSCs can be generated from adult and fetal hepatocytes including those with genetic diseases. Fetal hepatocytes reprogram much more efficiently than adult hepatocytes, although both could serve as useful sources of hiPSC-derived hepatocytes for basic research or transplantation.

  9. Fetal electrocardiogram (ECG) for fetal monitoring during labour.

    PubMed

    Neilson, James P

    2015-12-21

    Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average

  10. The use of non-invasive fetal electrocardiography in diagnosing second-degree fetal atrioventricular block.

    PubMed

    Lakhno, Igor; Behar, Joachim A; Oster, Julien; Shulgin, Vyacheslav; Ostras, Oleksii; Andreotti, Fernando

    2017-01-01

    Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.

  11. Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep.

    PubMed

    Koome, Miriam E; Bennet, Laura; Booth, Lindsea C; Davidson, Joanne O; Wassink, Guido; Gunn, Alistair Jan

    2014-01-01

    Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

  12. Diagnosis and management of heart failure in the fetus

    PubMed Central

    DAVEY, B.; SZWAST, A.; RYCHIK, J.

    2015-01-01

    Heart failure can be defined as the inability of the heart to sufficiently support the circulation. In the fetus, heart failure can be caused by a myriad of factors that include fetal shunting abnormalities, genetic cardiomyopathies, extracardiac malformations, arrhythmias and structural congenital heart disease. With advances in ultrasound has come the ability to characterize many complex conditions, previously poorly understood. Fetal echocardiography provides the tools necessary to evaluate and understand the various physiologies that contribute to heart failure in the fetus. In this review, we will explore the different mechanisms of heart failure in this unique patient population and highlight the role of fetal echocardiography in the current management of these conditions PMID:22992530

  13. The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

    PubMed Central

    Sucharov, Carmen C.; Helmke, Steve M.; Langer, Stephen J.; Perryman, M. Benjamin; Bristow, Michael; Leinwand, Leslie

    2004-01-01

    Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure. PMID:15367688

  14. The effect of maternal methadone use on the fetal heart pattern: a computerised CTG analysis.

    PubMed

    Navaneethakrishnan, R; Tutty, S; Sinha, C; Lindow, S W

    2006-08-01

    Using a computerised analysis, the cardiotocograph (CTG) from women who use methadone (n= 25) when compared with women who do not use methadone (n= 25) showed a significant reduction in the fetal heart baseline rate, with a significant reduction in number of accelerations and episodes of high variation. The short-term variation, number of decelerations and episodes of low variation were not different between the two groups. The time taken to meet the standardised criteria was not different, and it is possible that a computer-assisted CTG analysis could be more accurate than a naked eye interpretation.

  15. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

    PubMed

    Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

    2010-08-01

    Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

  16. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    PubMed

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

    PubMed

    Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

    2017-02-01

    Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

  18. Correlation of arterial fetal base deficit and lactate changes with severity of variable heart rate decelerations in the near-term ovine fetus.

    PubMed

    Ross, Michael G; Jessie, Marquis; Amaya, Kevin; Matushewski, Brad; Durosier, L Daniel; Frasch, Martin G; Richardson, Bryan S

    2013-04-01

    Recent guidelines classify variable decelerations without detail as to degree of depth. We hypothesized that variable deceleration severity is highly correlated with fetal base deficit accumulation. Seven near-term fetal sheep underwent a series of graded umbilical cord occlusions resulting in mild (30 bpm decrease), moderate (60 bpm decrease), or severe (decrease of 90 bpm to baseline <70 bpm) variable decelerations at 2.5 minute intervals. Mild, moderate, and severe variable decelerations increased fetal base deficit (0.21 ± 0.03, 0.27 ± 0.03, and 0.54 ± 0.09 mEq/L per minute) in direct proportion to severity. During recovery, fetal base deficit cleared at 0.12 mEq/L per minute. In this model, ovine fetuses can tolerate repetitive mild and moderate variable decelerations with minimal change in base deficit and lactate. In contrast, repetitive severe variable decelerations may result in significant base deficit increases, dependent on frequency. Modified guideline differentiation of mild/moderate vs severe variable decelerations may aid in the interpretation of fetal heart rate tracings and optimization of clinical management paradigms. Copyright © 2013 Mosby, Inc. All rights reserved.

  19. Fetal transesophageal echocardiography: clinical introduction as a monitoring tool during cardiac intervention in a human fetus.

    PubMed

    Kohl, T; Müller, A; Tchatcheva, K; Achenbach, S; Gembruch, U

    2005-12-01

    Because of insufficient imaging by maternal transabdominal fetal echocardiography (TAE) in a human fetus with aortic atresia, imperforate atrial septum and progressive cardiac failure, we assessed the feasibility of fetal transesophageal echocardiography (TEE) as a monitoring tool during fetal cardiac intervention at 24 + 6 weeks of gestation. Percutaneous fetoscopic intraesophageal deployment of the ultrasound catheter was achieved and did not result in any maternal or fetal complications. Fetal TEE permitted substantially clearer definition of fetal cardiac anatomy and intracardiac device manipulations than conventional maternal TAE. Despite the employment of various devices, no sufficiently large opening could be achieved within the atrial septum. Although the fetus tolerated the procedure remarkably well and satisfactory fetoplacental flow could be documented at the end of the procedure, the fetus died from progressive cardiac failure 3 days after the intervention. Fetoscopic TEE is feasible in the human fetus and permits substantially clearer definition of fetal cardiac anatomy and intracardiac manipulations than conventional maternal TAE. Based on the observation of spontaneous closure of multiple iatrogenic perforations of the atrial septum, specialized devices are required in order to improve the technical success rate of septoplasty methods and hence the survival odds of these high-risk patients.

  20. Human heart by art.

    PubMed

    Tamir, Abraham

    2012-11-01

    Heart is of great importance in maintaining the life of the body. Enough to stop working for a few minutes to cause death, and hence the great importance in physiology, medicine, and research. This fact was already emphasized in the Bible in the Book of Proverbs, chapter 4 verse 23: "Keep your heart with all diligence, for out of it is the wellspring of life." Art was able to demonstrate the heart from various aspects; realistically, as done by Leonardo de Vinci who demonstrated the halves of the heart and its blood vessels. Symbolically, as a source of life, the heart was demonstrated by the artist Mrs. Erlondeiel, as a caricature by Salvador Dali, as an open heart by Sawaya, etc. Finally, it should be emphasized that different demonstrations of the human heart by many artworks make this most important organ of our body (that cannot be seen from outside) more familiar and clearer to us. And this is the purpose of this article-to demonstrate the heart through a large number of artworks of different kinds.

  1. An Effective Technique for Enhancing an Intrauterine Catheter Fetal Electrocardiogram

    NASA Astrophysics Data System (ADS)

    Horner, Steven L.; Holls, William M.

    2003-12-01

    Physician can obtain fetal heart rate, electrophysiological information, and uterine contraction activity for determining fetal status from an intrauterine catheters electrocardiogram with the maternal electrocardiogram canceled. In addition, the intrauterine catheter would allow physicians to acquire fetal status with one non-invasive to the fetus biosensor as compared to invasive to the fetus scalp electrode and intrauterine pressure catheter used currently. A real-time maternal electrocardiogram cancellation technique of the intrauterine catheters electrocardiogram will be discussed along with an analysis for the methods effectiveness with synthesized and clinical data. The positive results from an original detailed subjective and objective analysis of synthesized and clinical data clearly indicate that the maternal electrocardiogram cancellation method was found to be effective. The resulting intrauterine catheters electrocardiogram from effectively canceling the maternal electrocardiogram could be used for determining fetal heart rate, fetal electrocardiogram electrophysiological information, and uterine contraction activity.

  2. Diurnal changes in the power spectral characteristics of eye movements and heart rate variability in the human fetus at term.

    PubMed

    Morokuma, S; Horimoto, N; Nakano, H

    2001-08-01

    It is well known that 1/f characteristics in power spectral patterns exist in various biological factors including heart rate variability. In the present study, we tried to elucidate the diurnal variation in spectral properties of eye movement and heart rate variability in the human fetus at term, via continuous 24-h observation of both these parameters. Studied were five uncomplicated fetuses at term. We observed eye movement and fetal heart rate (FHR) with real-time ultrasound and Doppler cardiotocograph, respectively, and analyzed the diurnal change in spectral properties, using the maximum entropy method. In four of five cases, the slope values of power spectra for both eye movement frequency and FHR, ranging approximately between 0.5 and 1.8, indicated diurnal variation, where the slopes tended to have high values during the day and low values at night. These findings suggest that, in the human fetus at term, eye movement and FHR are under the control of a common central mechanism, and this center changes its complexity as seen through diurnal rhythm.

  3. Antiinflammatory Effects of Budesonide in Human Fetal Lung.

    PubMed

    Barrette, Anne Marie; Roberts, Jessica K; Chapin, Cheryl; Egan, Edmund A; Segal, Mark R; Oses-Prieto, Juan A; Chand, Shreya; Burlingame, Alma L; Ballard, Philip L

    2016-11-01

    Lung inflammation in premature infants contributes to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without the apparent adverse effects that occur with systemic dexamethasone therapy. Our objective was to determine budesonide potency, stability, and antiinflammatory effects in human fetal lung. We cultured explants of second-trimester fetal lung with budesonide or dexamethasone and used microscopy, immunoassays, RNA sequencing, liquid chromatography/tandem mass spectrometry, and pulsating bubble surfactometry. Budesonide suppressed secreted chemokines IL-8 and CCL2 (MCP-1) within 4 hours, reaching a 90% decrease at 12 hours, which was fully reversed 72 hours after removal of the steroid. Half-maximal effects occurred at 0.04-0.05 nM, representing a fivefold greater potency than for dexamethasone. Budesonide significantly induced 3.6% and repressed 2.8% of 14,500 sequenced mRNAs by 1.6- to 95-fold, including 119 genes that contribute to the glucocorticoid inflammatory transcriptome; some are known targets of nuclear factor-κB. By global proteomics, 22 secreted inflammatory proteins were hormonally regulated. Two glucocorticoid-regulated genes of interest because of their association with lung disease are CHI3L1 and IL1RL1. Budesonide retained activity in the presence of surfactant and did not alter its surface properties. There was some formation of palmitate-budesonide in lung tissue but no detectable metabolism to inactive 16α-hydroxy prednisolone. We concluded that budesonide is a potent and stable antiinflammatory glucocorticoid in human fetal lung in vitro, supporting a beneficial antiinflammatory response to lung-targeted budesonide:surfactant treatment of infants for the prevention of BPD.

  4. Are we (mis)guided by current guidelines on intrapartum fetal heart rate monitoring? Case for a more physiological approach to interpretation.

    PubMed

    Ugwumadu, A

    2014-08-01

    Original interpretations of fetal heart rate (FHR) patterns equated FHR decelerations with 'fetal distress', requiring expeditious delivery. This simplistic interpretation is still implied in our clinical guidelines despite 40 years of increasing understanding of the behaviour and regulation of the fetal cardiovascular system during labour. The physiological basis of FHR responses and adaptations to oxygen deprivation is de-emphasised, whilst generations of obstetricians and midwives are trained to focus on, and classify, the morphological appearances of decelerations into descriptive categories, with no attempt to understand how the fetus defends itself and compensates for intrapartum hypoxic ischaemic insults, or the patterns that suggest progressive loss of compensation. Consequently, there is a lack of confidence, marked variation in FHR interpretation, defensive practices, unnecessary operative interventions, and a failure to recognise abnormal FHR patterns, resulting in adverse outcomes and expensive litigation. © 2014 Royal College of Obstetricians and Gynaecologists.

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

    PubMed

    Verdurmen, Kim M J; Lempersz, Carlijn; Vullings, Rik; Schroer, Christian; Delhaas, Tammo; van Laar, Judith O E H; Oei, S Guid

    2016-08-17

    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. 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. 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).

  6. Trans-abdominal monitoring of fetal arterial blood oxygenation using pulse oximetry

    NASA Astrophysics Data System (ADS)

    Zourabian, Anna; Siegel, Andrew M.; Chance, Britton; Ramanujam, Nirmala; Rode, Martha; Boas, David A.

    2000-10-01

    Pulse oximetry (oxygen saturation monitoring) has markedly improved medical care in many fields, including anesthesiology, intensive care, and newborn intensive care. In obstetrics, fetal heart rate monitoring remains the standard for intrapartum assessment of fetal well being. Fetal oxygen saturation monitoring is a new technique currently under development. It is potentially superior to electronic fetal heart rate monitoring (cardiotocography) because it allows direct assessment of both the fetal oxygen status and fetal tissue perfusion. Here we present the analysis for determining the most optimal wavelength selection for pulse oximetry. The wavelengths we chose as the most optimal are the first in the range of 670 - 720 nm and the second in the range of 825 - 925 nm. Further, we discuss the possible systematic errors during our measurements and their contribution to the obtained saturation results. We present feasibility studies for fetal pulse oximetry, monitored noninvasively through the maternal abdomen. Our preliminary experiments show that the fetal pulse can be discriminated from the maternal pulse and thus, in principle, the fetal arterial oxygen saturation can be obtained. We present the methodology for obtaining these data, and discuss the dependence of our measurements on the fetal position with respect to the optode assembly.

  7. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    PubMed Central

    Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

    2016-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

  8. Regulation of fibrillins and modulators of TGFβ in fetal bovine and human ovaries.

    PubMed

    Bastian, Nicole A; Bayne, Rosemary A; Hummitzsch, Katja; Hatzirodos, Nicholas; Bonner, Wendy M; Hartanti, Monica D; Irving-Rodgers, Helen F; Anderson, Richard A; Rodgers, Raymond J

    2016-08-01

    Fibrillins 1-3 are stromal extracellular matrix proteins that play important roles in regulating TGFβ activity, which stimulates fibroblasts to proliferate and synthesize collagen. In the developing ovary, the action of stroma is initially necessary for the formation of ovigerous cords and subsequently for the formation of follicles and the surface epithelium of the ovary. FBN3 is highly expressed only in early ovarian development and then it declines. In contrast, FBN1 and 2 are upregulated in later ovarian development. We examined the expression of FBN1-3 in bovine and human fetal ovaries. We used cell dispersion and monolayer culture, cell passaging and tissue culture. Cells were treated with growth factors, hormones or inhibitors to assess the regulation of expression of FBN1-3 When bovine fetal ovarian tissue was cultured, FBN3 expression declined significantly. Treatment with TGFβ-1 increased FBN1 and FBN2 expression in bovine fibroblasts, but did not affect FBN3 expression. Additionally, in cultures of human fetal ovarian fibroblasts (9-17weeks gestational age), the expression of FBN1 and FBN2 increased with passage, whereas FBN3 dramatically decreased. Treatment with activin A and a TGFβ family signaling inhibitor, SB431542, differentially regulated the expression of a range of modulators of TGFβ signaling and of other growth factors in cultured human fetal ovarian fibroblasts suggesting that TGFβ signaling is differentially involved in the regulation of ovarian fibroblasts. Additionally, since the changes in FBN1-3 expression that occur in vitro are those that occur with increasing gestational age in vivo, we suggest that the fetal ovarian fibroblasts mature in vitro. © 2016 Society for Reproduction and Fertility.

  9. Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support.

    PubMed

    Giri, Shibashish; Bader, Augustinus

    2014-09-01

    Generation of genetically stable and non-tumoric immortalization cell line from primary cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. It is now universal acceptance that immortalization of human fetal hepatocytes based on recent advances of telomerase biology and oncogene, lead to unlimited population doubling could be the possible source for bioartificial liver device. Immortalization of human fetal hepatocytes cell line by ectopic expression of human telomerase reverse transcriptase (hTERT), human papilloma virus gene (E7) and simian virus 40 large T (SV40 T) antigens is main goal of present study. We used an inducible system containing human telomerase and E7, both of which are cloned into responder constructs controlled by doxycycline transactivator. We characterized the immortalized human fetal hepatocyte cells by analysis of green fluorescent cells (GFP) positive cells using flow cytometry (FACs) cell sorting and morphology, proliferative rate and antigen expression by immunohistochemical analysis. In addition to we analysized lactate formation, glucose consumption, albumin secretion and urea production of immortalized human fetal hepatocyte cells. After 25 attempts for transfection of adult primary hepatocytes by human telomerase and E7 to immortalize them, none of the transfection systems resulted in the production of a stable, proliferating cell line. Although the transfection efficiency was more than 70% on the first day, the vast majority of the transfected hepatocytes lost their signal within the first 5-7 days. The remaining transfected hepatocytes persisted for 2-4 weeks and divided one or two times without forming a clone. After 10 attempts of transfection human fetal hepatocytes using the same transfection system, we obtained one stable human fetal hepatocytes cell line which was able albumin secretion urea production and glucose consumption. We established a

  10. Detection and Processing Techniques of FECG Signal for Fetal Monitoring

    PubMed Central

    2009-01-01

    Fetal electrocardiogram (FECG) signal contains potentially precise information that could assist clinicians in making more appropriate and timely decisions during labor. The ultimate reason for the interest in FECG signal analysis is in clinical diagnosis and biomedical applications. The extraction and detection of the FECG signal from composite abdominal signals with powerful and advance methodologies are becoming very important requirements in fetal monitoring. The purpose of this review paper is to illustrate the various methodologies and developed algorithms on FECG signal detection and analysis to provide efficient and effective ways of understanding the FECG signal and its nature for fetal monitoring. A comparative study has been carried out to show the performance and accuracy of various methods of FECG signal analysis for fetal monitoring. Finally, this paper further focused some of the hardware implementations using electrical signals for monitoring the fetal heart rate. This paper opens up a passage for researchers, physicians, and end users to advocate an excellent understanding of FECG signal and its analysis procedures for fetal heart rate monitoring system. PMID:19495912

  11. Cardiotocography versus intermittent auscultation of fetal heart on admission to labour ward for assessment of fetal wellbeing.

    PubMed

    Devane, Declan; Lalor, Joan G; Daly, Sean; McGuire, William; Smith, Valerie

    2012-02-15

    The admission cardiotocograph (CTG) is a commonly used screening test consisting of a short (usually 20 minutes) recording of the fetal heart rate (FHR) and uterine activity performed on the mother's admission to the labour ward. To compare the effects of admission CTG with intermittent auscultation of the FHR on maternal and infant outcomes for pregnant women without risk factors on their admission to the labour ward. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 May 2011) (CENTRAL) (The Cochrane Library 2011 Issue 2 of 4), MEDLINE (1966 to 17 May 2011), CINAHL (1982 to 17 May 2011), Dissertation Abstracts (1980 to 17 May 2011) and the reference list of retrieved papers. All randomised and quasi-randomised trials comparing admission CTG with intermittent auscultation of the FHR for pregnant women between 37 and 42 completed weeks of pregnancy and considered to be at low risk of intrapartum fetal hypoxia and of developing complications during labour. Two authors independently assessed trial eligibility and quality, and extracted data. Data were checked for accuracy. We included four trials involving more than 13,000 women. All four studies included women in labour. Overall, the studies were at low risk of bias. Although not statistically significant using a strict P < 0.05 criterion, data are consistent with women allocated to admission CTG having, on average, a higher probability of an increase in incidence of caesarean section than women allocated to intermittent auscultation (risk ratio (RR) 1.20, 95% confidence interval (CI) 1.00 to 1.44, four trials, 11,338 women, T² = 0.00, I² = 0%). There was no significant difference in the average treatment effect across included trials between women allocated to admission CTG and women allocated to intermittent auscultation in instrumental vaginal birth (RR 1.10, 95% CI 0.95 to 1.27, four trials, 11,338 women, T² = 0.01, I² = 38%) and fetal and neonatal deaths (RR 1.01, 95% CI 0.30 to 3

  12. Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.

    1987-06-01

    To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from lambdagt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. Inmore » RNA blots of poly(A)/sup +/ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species.« less

  13. Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development

    PubMed Central

    Vasung, Lana; Lepage, Claude; Radoš, Milan; Pletikos, Mihovil; Goldman, Jennifer S.; Richiardi, Jonas; Raguž, Marina; Fischi-Gómez, Elda; Karama, Sherif; Huppi, Petra S.; Evans, Alan C.; Kostovic, Ivica

    2016-01-01

    The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13–40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the

  14. Fetal in vivo continuous cardiovascular function during chronic hypoxia

    PubMed Central

    Allison, B. J.; Brain, K. L.; Niu, Y.; Kane, A. D.; Herrera, E. A.; Thakor, A. S.; Botting, K. J.; Cross, C. M.; Itani, N.; Skeffington, K. L.; Beck, C.

    2016-01-01

    Key points The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism. Abstract Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean PaO2 levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery

  15. Development and significance of a fetal electrocardiogram recorded by signal-averaged high-amplification electrocardiography.

    PubMed

    Hayashi, Risa; Nakai, Kenji; Fukushima, Akimune; Itoh, Manabu; Sugiyama, Toru

    2009-03-01

    Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

  16. Antiinflammatory Effects of Budesonide in Human Fetal Lung

    PubMed Central

    Barrette, Anne Marie; Roberts, Jessica K.; Chapin, Cheryl; Egan, Edmund A.; Segal, Mark R.; Oses-Prieto, Juan A.; Chand, Shreya; Burlingame, Alma L.

    2016-01-01

    Lung inflammation in premature infants contributes to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without the apparent adverse effects that occur with systemic dexamethasone therapy. Our objective was to determine budesonide potency, stability, and antiinflammatory effects in human fetal lung. We cultured explants of second-trimester fetal lung with budesonide or dexamethasone and used microscopy, immunoassays, RNA sequencing, liquid chromatography/tandem mass spectrometry, and pulsating bubble surfactometry. Budesonide suppressed secreted chemokines IL-8 and CCL2 (MCP-1) within 4 hours, reaching a 90% decrease at 12 hours, which was fully reversed 72 hours after removal of the steroid. Half-maximal effects occurred at 0.04–0.05 nM, representing a fivefold greater potency than for dexamethasone. Budesonide significantly induced 3.6% and repressed 2.8% of 14,500 sequenced mRNAs by 1.6- to 95-fold, including 119 genes that contribute to the glucocorticoid inflammatory transcriptome; some are known targets of nuclear factor-κB. By global proteomics, 22 secreted inflammatory proteins were hormonally regulated. Two glucocorticoid-regulated genes of interest because of their association with lung disease are CHI3L1 and IL1RL1. Budesonide retained activity in the presence of surfactant and did not alter its surface properties. There was some formation of palmitate-budesonide in lung tissue but no detectable metabolism to inactive 16α-hydroxy prednisolone. We concluded that budesonide is a potent and stable antiinflammatory glucocorticoid in human fetal lung in vitro, supporting a beneficial antiinflammatory response to lung-targeted budesonide:surfactant treatment of infants for the prevention of BPD. PMID:27281349

  17. Persistent Infection of Human Fetal Endothelial Cells with Rubella Virus

    PubMed Central

    Perelygina, Ludmila; Zheng, Qi; Metcalfe, Maureen; Icenogle, Joseph

    2013-01-01

    Cardiovascular abnormalities are the leading cause of neonatal death among patients with congenital rubella syndrome (CRS). Although persistence of rubella virus (RV) in fetal endothelium has been repeatedly suggested as a possible cause of cardiovascular birth defects, evidence of the permissiveness of fetal endothelial cells to RV is lacking. In this study we evaluated the ability of RV to infect and persist in primary fetal endothelial cells derived from human umbilical vein (HUVEC). We found that wild type (wt) low passage clinical RV productively infected HUVEC cultures without producing cytopathology or ultrastructural changes. RV did not inhibit host cell protein synthesis, cell proliferation, or interfere with the cell cycle. Persistently infected cultures were easily established at low and high multiplicities of infection (MOI) with both laboratory and wt clinical RV strains. However, synchronous infections of entire HUVEC monolayers were only observed with clinical RV strains. The release of infectious virions into media remained at consistently high levels for several subcultures of infected HUVEC. The results indicate that macrovascular fetal endothelial cells are highly permissive to RV and allow slow persistent RV replication. The findings provide more evidence for the suggestion that vascular pathologies in CRS are triggered by persistent rubella virus infection of the endothelium. PMID:23940821

  18. The effects of different concentrations of cocoa in the chocolate intaken by the mother on fetal heart rate.

    PubMed

    Buscicchio, Giorgia; Lorenzi, Sara; Tranquilli, Andrea Luigi

    2013-10-01

    To analyze the effects of different concentrations (30% and 80%) of cocoa on fetal heart rate (FHR). One hundred pregnant women with uncomplicated gestation, matched for age and parity, underwent computerized FHR recording before and after the consumption of 30 g of 30% and 80% cocoa chocolate. After 1 week, those who had received 30% were shifted to 80% and vice versa to have a crossover. Computerized cardiotocography parameters (contractions, fetal movements, baseline FHR, accelerations greater than 15 bpm for 15 s, number of decelerations, minutes of high variability, short term variability in ms) were recorded and expressed as mean and SD. The differences were tested for statistical significance using the paired t test, with the significance at p < 0.05. The percent change after chocolate intake for accelerations and short-term FHR variation was calculated. The number of fetal movements, accelerations, the duration of episodes of high variation and the short-term FHR variation were significantly higher (p < 0.0001) after 80% cocoa intake. After 30% cocoa chocolate intake, only the number of accelerations was significantly increased. The percent change of the number of accelerations and the short-term FHR variation were significantly higher after 80% cocoa chocolate maternal intake. Maternal intake of dark chocolate has a stimulating action on fetal reactivity. The effect is more marked with high concentrations (80%) of cocoa. This finding is likely due to the pharmacological action of theobromine, a methilxanthine present in cocoa.

  19. GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation.

    PubMed

    Larijani, Bagher; Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

    2015-01-01

    Stem cell therapy seems a promising avenue in regenerative medicine. Within various stem cells, mesenchymal stem cells have progressively used for cellular therapy. Because of the age-related decreasing in the frequency and differentiating capacity of adult MSCs, fetal tissues such as fetal liver, lung, pancreas, spleen, etc. have been introduced as an alternative source of MSCs for cellular therapy. On the other hand, using stem cells as advanced therapy medicinal products, must be performed in compliance with cGMP as a quality assurance system to ensure the safety, quality, and identity of cell products during translation from the basic stem cell sciences into clinical cell transplantation. In this chapter the authors have demonstrated the manufacturing of GMP-grade human fetal liver-derived mesenchymal stem cells.

  20. Theoretical considerations to optimize transabdominal monitoring of fetal arterial blood oxygenation using pulse oximetry

    NASA Astrophysics Data System (ADS)

    Zourabian, Anna; Boas, David A.

    2001-06-01

    Pulse oximetry (oxygen saturation monitoring) has markedly improved medical care in many fields, including anesthesiology, intensive care, and newborn intensive care. In obstetrics, fetal heart rate monitoring remains the standard for intrapartum assessment of fetal well being. Fetal oxygen saturation monitoring is a new technique currently under development. It is potentially superior to electronic fetal heart rate monitoring (cardiotocography) because it allows direct assessment of both fetal oxygen status and fetal tissue perfusion. Here we present the analysis for determining the most optimal wavelength selection for pulse oximetry. The wavelengths we chose as the most optimal are: the first in the range of 670-720nm and the second in the range of 825-925nm. Further we discuss the possible systematic errors during our measurements, and their contribution to the obtained saturation results.

  1. Signal separation by nonlinear projections: The fetal electrocardiogram

    NASA Astrophysics Data System (ADS)

    Schreiber, Thomas; Kaplan, Daniel T.

    1996-05-01

    We apply a locally linear projection technique which has been developed for noise reduction in deterministically chaotic signals to extract the fetal component from scalar maternal electrocardiographic (ECG) recordings. Although we do not expect the maternal ECG to be deterministic chaotic, typical signals are effectively confined to a lower-dimensional manifold when embedded in delay space. The method is capable of extracting fetal heart rate even when the fetal component and the noise are of comparable amplitude. If the noise is small, more details of the fetal ECG, like P and T waves, can be recovered.

  2. Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues.

    PubMed Central

    Prody, C A; Zevin-Sonkin, D; Gnatt, A; Goldberg, O; Soreq, H

    1987-01-01

    To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase (BtChoEase; EC 3.1.1.8) and Torpedo electric organ "true" acetylcholinesterase (AcChoEase; EC 3.1.1.7). Using these probes, we isolated several cDNA clones from lambda gt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A)+ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These findings demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species. Images PMID:3035536

  3. Fetal Neurobehavioral Development: A Tale of Two Cities.

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; Caulfield, Laura; Costigan, Kathleen A.; Merialdi, Mario; Nguyen, Ruby H. N.; Zavaleta, Nelly; Gurewitsch, Edith D.

    2004-01-01

    Longitudinal neurobehavioral development was examined in 237 fetuses of low-risk pregnancies from 2 distinct populations-Baltimore, Maryland, and Lima, Peru-at 20, 24, 28, 32, 36, and 38 weeks gestation. Data were based on digitized Doppler-based fetal heart rate (FHR) and fetal movement (FM). In both groups, FHR declined while variability,…

  4. Recent advances in the prenatal interrogation of the human fetal genome.

    PubMed

    Hui, Lisa; Bianchi, Diana W

    2013-02-01

    The amount of genetic and genomic information obtainable from the human fetus during pregnancy is accelerating at an unprecedented rate. Two themes have dominated recent technological advances in prenatal diagnosis: interrogation of the fetal genome in increasingly high resolution and the development of non-invasive methods of fetal testing using cell-free DNA in maternal plasma. These two areas of advancement have now converged with several recent reports of non-invasive assessment of the entire fetal genome from maternal blood. However, technological progress is outpacing the ability of the healthcare providers and patients to incorporate these new tests into existing clinical care, and further complicates many of the economic and ethical dilemmas in prenatal diagnosis. This review summarizes recent work in this field and discusses the integration of these new technologies into the clinic and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

    PubMed Central

    Ishimoto, Hitoshi

    2011-01-01

    Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

  6. Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: a controlled clinical trial.

    PubMed

    Neldam, S; Osler, M; Hansen, P K; Nim, J; Smith, S F; Hertel, J

    1986-10-01

    In a prospective clinical randomized investigation 487 women had the condition of the fetus during labour supervised by means of stethoscope (AUS), while 482 women went through labour under surveillance of electronic fetal monitoring, cardiotocography (EFM). 349 women refused to participate in the investigation (NAI) and had delivery conducted according to the normal procedures of the department (70% AUS, 30% EFM). Significantly more pathological fetal heart rate patterns (FHR) were found in the EFM group compared to the AUS group in both the first and the second stage of labour. As a result significantly more vacuum extractions were performed in the EFM group than in the AUS group, while no statistical difference was found between the groups in the incidence of acute cesarean sections carried out for asphyxia. One case of intrapartum death occurred in the AUS group. No differences were found in Apgar scores after 1 and 5 min or in neonatal morbidity at examination on the 2nd and 5th days after delivery. A tendency towards more biochemically compromised children was found in the AUS group. The specificity for both methods was found to be acceptably high (80%), while the predictive value for both methods was low (50%). More research is therefore urgently needed to evaluate supplementary investigations and parameters for the evaluation of the intrapartum fetal condition.

  7. Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure.

    PubMed

    Lear, Christopher A; Davidson, Joanne O; Booth, Lindsea C; Wassink, Guido; Galinsky, Robert; Drury, Paul P; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair J

    2014-08-15

    Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg(-1)·24 h(-1) for a further 96 h) or the same volume of saline (n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV. Copyright © 2014 the American Physiological Society.

  8. Increased cardiovascular risk in adult survivors of fetal anemia

    PubMed Central

    Wallace, Alexandra H; Dalziel, Stuart R; Cowan, Brett R; Young, Alistair A; Thornburg, Kent L; Harding, Jane E

    2017-01-01

    Importance Brief exposure to intrauterine anemia doubles coronary conductance but increases susceptibility to cardiac ischemic injury in adult sheep. The effects of fetal anemia in humans on cardiovascular outcomes in adulthood has not previously been investigated. Objective To compare cardiovascular disease risk factors in adult survivors of fetal anemia with that of non-anemic siblings. Design A retrospective observational cohort study (The Fetal Anemia Study), undertaken between January 1, 2010 and July 31, 2012. Setting Tertiary hospital, Auckland, New Zealand. Participants Exposed participants (n=95) were adults who received intrauterine transfusion at National Women’s Hospital, Auckland between 1963–92 for treatment of severe anemia due to rhesus disease, resident in New Zealand and with a suitable non-anemic sibling. Unexposed participants (n=92) were siblings of exposed participants. Of potentially eligible exposed participants, 86% agreed to participate. Exposure Severe fetal anemia secondary to rhesus disease vs no intrauterine anemia. Main Outcomes Height, weight, body mass index, blood pressure, fasting lipid concentrations, heart rate variability, and cardiac MRI-determined left ventricular function and myocardial blood flow at rest, with cold pressor stress, and adenosine-induced vasodilation. Participant characteristics included gestation and weight at birth, age, and comorbid disease. Results Exposed participants were younger than unexposed (mean±SD: 33.7±9.3 vs 40.1±10.9 years, p<0.001), born earlier (34.3±1.7 vs 39.5±2.1 weeks, p<0.001), had decreased high-density lipoprotein concentration (−0.12 mmol/l, −0.24 to 0.00, p=0.04), and increased low to high frequency heart rate variability ratio (ratio of geometric means 1.53, 1.04 to 2.25, p=0.03). Exposed participants also had smaller left ventricular volumes (end diastolic volume/body surface area, difference between adjusted means −6.09 ml, 95% CI −9.75 to −2.42, p=0

  9. A beta1-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction.

    PubMed

    Sucharov, Carmen C; Mariner, Peter D; Nunley, Karin R; Long, Carlin; Leinwand, Leslie; Bristow, Michael R

    2006-09-01

    Beta-adrenergic signaling plays an important role in the natural history of dilated cardiomyopathies. Chronic activation of beta-adrenergic receptors (beta1-AR and beta2-AR) during periods of cardiac stress ultimately harms the failing heart by mechanisms that include alterations in gene expression. Here, we show that stimulation of beta-ARs with isoproterenol in neonate rat ventricular myocytes causes a "fetal" response in the relative activities of the human cardiac fetal and/or adult gene promoters that includes repression of the human and rat alpha-myosin heavy chain (alpha-MyHC) promoters with simultaneous activation of the human atrial natriuretic peptide (ANP) and rat beta-MyHC promoters. We also show that the promoter changes correlate with changes in endogenous gene expression as measured by mRNA expression. Furthermore, we show that these changes are specifically mediated by the beta1-AR, but not the beta2-AR, and are independent of alpha1-AR stimulation. We also demonstrate that the fetal gene response is independent of cAMP and protein kinase A, whereas inhibition of Ca2+/calmodulin-dependent protein kinase (CaMK) pathway blocks isoproterenol-mediated fetal gene program induction. Finally, we show that induction of the fetal program is dependent on activation of the L-type Ca2+ channel. We conclude that in neonatal rat cardiac myocytes, agonist-occupied beta1-AR mobilizes Ca2+ stores to activate fetal gene induction through cAMP independent pathways that involve CaMK.

  10. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in anmore » apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to

  11. Prediction of Fetal Darunavir Exposure by Integrating Human Ex-Vivo Placental Transfer and Physiologically Based Pharmacokinetic Modeling.

    PubMed

    Schalkwijk, Stein; Buaben, Aaron O; Freriksen, Jolien J M; Colbers, Angela P; Burger, David M; Greupink, Rick; Russel, Frans G M

    2017-07-25

    Fetal antiretroviral exposure is usually derived from the cord-to-maternal concentration ratio. This static parameter does not provide information on the pharmacokinetics in utero, limiting the assessment of a fetal exposure-effect relationship. The aim of this study was to incorporate placental transfer into a pregnancy physiologically based pharmacokinetic model to simulate and evaluate fetal darunavir exposure at term. An existing and validated pregnancy physiologically based pharmacokinetic model of maternal darunavir/ritonavir exposure was extended with a feto-placental unit. To parameterize the model, we determined maternal-to-fetal and fetal-to-maternal darunavir/ritonavir placental clearance with an ex-vivo human cotyledon perfusion model. Simulated maternal and fetal pharmacokinetic profiles were compared with observed clinical data to qualify the model for simulation. Next, population fetal pharmacokinetic profiles were simulated for different maternal darunavir/ritonavir dosing regimens. An average (±standard deviation) maternal-to-fetal cotyledon clearance of 0.91 ± 0.11 mL/min and fetal-to-maternal clearance of 1.6 ± 0.3 mL/min was determined (n = 6 perfusions). Scaled placental transfer was integrated into the pregnancy physiologically based pharmacokinetic model. For darunavir 600/100 mg twice a day, the predicted fetal maximum plasma concentration, trough concentration, time to maximum plasma concentration, and half-life were 1.1, 0.57 mg/L, 3, and 21 h, respectively. This indicates that the fetal population trough concentration is higher or around the half-maximal effective darunavir concentration for a resistant virus (0.55 mg/L). The results indicate that the population fetal exposure after oral maternal darunavir dosing is therapeutic and this may provide benefits to the prevention of mother-to-child transmission of human immunodeficiency virus. Moreover, this integrated approach provides a tool to prevent fetal toxicity or

  12. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  13. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE PAGES

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; ...

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  14. Functional adaptations of the coronary microcirculation to anaemia in fetal sheep.

    PubMed

    Jonker, Sonnet S; Davis, Lowell; Soman, Divya; Belcik, J Todd; Davidson, Brian P; Atkinson, Tamara M; Wilburn, Adrienne; Louey, Samantha; Giraud, George D; Lindner, Jonathan R

    2016-11-01

    In fetuses, chronic anaemia stimulates cardiac growth; simultaneously, blood flow to the heart muscle itself is increased, and reserve blood flow capacity of the coronary vascular bed is preserved. Here we examined functional adaptations of the capillaries and small blood vessels responsible for delivering oxygen to the anaemic fetal heart muscle using contrast-enhanced echocardiography. We demonstrate that coronary microvascular flux rate doubled in anaemic fetuses compared to control fetuses, both at rest and during maximal flow, suggesting reduced microvascular resistance consistent with capillary widening. Cardiac fractional microvascular blood volume was not greater in anaemic fetuses, suggesting that growth of new microvascular vessels does not contribute to the increased flow per volume of myocardium. These unusual changes in microvascular function during anaemia may indicate novel adaptive strategies in the fetal heart. Fetal anaemia causes cardiac adaptations that have immediate and life-long repercussions on heart function and health. It is known that resting and maximal coronary conductance both increase during chronic fetal anaemia, but the coronary microvascular changes responsible for the adaptive response are unknown. Until recently, technical limitations have prevented quantifying functional capillary-level adaptations in the in vivo fetal heart. Our objective was to characterise functional microvascular adaptations in chronically anaemic fetal sheep. Chronically instrumented fetuses were randomized to a control group (n = 11) or were made anaemic by isovolumetric haemorrhage (n = 12) for 1 week prior to myocardial contrast echocardiography at 85% of gestation. Anaemia augmented cardiac mass by 23% without changing body weight. In anaemic fetuses, microvascular blood flow per volume of myocardium was twice that of control fetuses at rest, during vasodilatory hyperaemia, and during hyperaemia plus increased aortic pressure. The elevated blood

  15. Intermittent auscultation of fetal heart rate during labour - a widely accepted technique for low risk pregnancies: but are the current national guidelines robust and practical?

    PubMed

    Sholapurkar, S L

    2010-01-01

    Intermittent auscultation of fetal heart rate is an accepted practice in low risk labours in many countries. National guidelines on intrapartum fetal monitoring were critically reviewed regarding timing and frequency of intermittent auscultation. Hypothetical but plausible examples are presented to illustrate that it may be possible to miss significant fetal distress with strict adherence to current guidelines. Opinion is forwarded that intermittent auscultation should be performed for 60 seconds before and after three contractions over about 10 min every half an hour in the first stage of labour. Reasons are put forward to show how this could be more practical and patient friendly and at the same time could improve detection of fetal distress. The current recommendation of intermittent auscultation every 15 min in the first stage is associated with poor compliance and leads to unnecessary burden, stress and medicolegal liability for birth attendants. Modification of current national guidelines would be desirable.

  16. MYSTERIES OF THE HUMAN FETUS REVEALED

    PubMed Central

    SANDMAN, CURT A

    2015-01-01

    The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Lacey's, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk.. PMID:26303720

  17. MYSTERIES OF THE HUMAN FETUS REVEALED.

    PubMed

    Sandman, Curt A

    2015-09-01

    The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al. open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Laceys, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk. © 2015 The Society for Research in Child Development, Inc.

  18. Dynamic classification of fetal heart rates by hierarchical Dirichlet process mixture models.

    PubMed

    Yu, Kezi; Quirk, J Gerald; Djurić, Petar M

    2017-01-01

    In this paper, we propose an application of non-parametric Bayesian (NPB) models for classification of fetal heart rate (FHR) recordings. More specifically, we propose models that are used to differentiate between FHR recordings that are from fetuses with or without adverse outcomes. In our work, we rely on models based on hierarchical Dirichlet processes (HDP) and the Chinese restaurant process with finite capacity (CRFC). Two mixture models were inferred from real recordings, one that represents healthy and another, non-healthy fetuses. The models were then used to classify new recordings and provide the probability of the fetus being healthy. First, we compared the classification performance of the HDP models with that of support vector machines on real data and concluded that the HDP models achieved better performance. Then we demonstrated the use of mixture models based on CRFC for dynamic classification of the performance of (FHR) recordings in a real-time setting.

  19. Dynamic classification of fetal heart rates by hierarchical Dirichlet process mixture models

    PubMed Central

    Yu, Kezi; Quirk, J. Gerald

    2017-01-01

    In this paper, we propose an application of non-parametric Bayesian (NPB) models for classification of fetal heart rate (FHR) recordings. More specifically, we propose models that are used to differentiate between FHR recordings that are from fetuses with or without adverse outcomes. In our work, we rely on models based on hierarchical Dirichlet processes (HDP) and the Chinese restaurant process with finite capacity (CRFC). Two mixture models were inferred from real recordings, one that represents healthy and another, non-healthy fetuses. The models were then used to classify new recordings and provide the probability of the fetus being healthy. First, we compared the classification performance of the HDP models with that of support vector machines on real data and concluded that the HDP models achieved better performance. Then we demonstrated the use of mixture models based on CRFC for dynamic classification of the performance of (FHR) recordings in a real-time setting. PMID:28953927

  20. Lens artifacts in human fetal eyes - the challenge of interpreting the histomorphology of human fetal lenses.

    PubMed

    Herwig, Martina C; Müller, Annette M; Klarmann-Schulz, Ute; Holz, Frank G; Loeffler, Karin U

    2014-01-01

    Evaluation of the lens, including cataractous changes, is often of paramount importance in the classification of fetal syndromes or forensic questions. On histology, the crystalline lens is - especially in fetal and infant eyes - an organ susceptible to numerous artifacts. Thus, the aim of our study was to study various factors (including fixatives) that might have an impact on lens histomorphology. Twenty eyes from ten fetuses (formalin fixation: n = 10, glutaraldehyde fixation: n = 10), matched for gestational age and abortion (spontaneous vs. induced), were investigated macroscopically and by light microscopy. Sections were stained with routine hematoxylin & eosin (H&E), and periodic acid schiff (PAS). The age of the fetal eyes ranged from 15 to 36 weeks of gestation. Lens artifacts were analyzed and compared to fetal and adult lenses with definitive cataractous changes. In addition, 34 eyes from 27 fetuses with trisomy 21 were investigated for lens changes. All lenses showed artifacts of varying extent, in particular globules, vacuoles, clefts, anterior/posterior capsular separation, subcapsular proteinaceous material, fragmentation of the lens capsule/epithelium, and a posterior umbilication. Glutaraldehyde-fixed lenses displayed less artifacts compared to those fixed in formalin. Slight differences in the appearance of artifacts were found dependent on the fixative (formaldehyde vs glutaraldehyde) and the kind of abortion (iatrogenous vs spontaneous). The gestational age did not have a significant influence on the type and extent of lens artifacts. The lenses from fetuses with trisomy 21 displayed similar lens artifacts with no specific findings. Alterations in fetal lens morphology are extremely frequent and variable. These artifacts have to be carefully taken into account when interpreting post-mortem findings. Thus, the postmortem diagnosis of a fetal cataract should be made with great caution, and should include, in adherence to our proposed

  1. Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: a descriptive study.

    PubMed

    Walraven, M; Beelen, R H J; Ulrich, M M W

    2015-05-01

    TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce. The aim of this study was to compare the canonical TGF-β signaling in unwounded human fetal and adult skin. Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy skin. All components of the canonical TGF-β pathway were present in unwounded fetal skin. Compared to adult skin, fetal skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and adult skin. This descriptive study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and adult skin. The findings of this study can be a starting point for further research into the role of TGF-β signaling in scarless healing. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Zika virus propagation and release in human fetal astrocytes can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869.

    PubMed

    Huang, Yunlong; Li, Yuju; Zhang, Hainan; Zhao, Runze; Jing, Ran; Xu, Yinghua; He, Miao; Peer, Justin; Kim, Yeong C; Luo, Jiangtao; Tong, Zenghan; Zheng, Jialin

    2018-01-01

    Zika virus (ZIKV) is a neurotrophic flavivirus that is capable of infecting humans, leading to brain abnormalities during fetal development. The ZIKV infectivity in neural target cells remains poorly understood. Here, we found that ZIKV specifically infected glial fibrillary acidic protein- and S100B-positive primary human astrocytes derived from fetal brains. In contrast, neuron-specific Class III β-tubulin (TuJ1)-positive neurons in the astrocyte cultures and SOX2-positive neural progenitor cells derived from the fetal brains were less susceptible to ZIKV infection compared with astrocytes. The infected astrocytes released competent viral particles and manifested programmed cell death with a progressive cytopathic effect. Interestingly, ZIKV infection in human fetal astrocytes induced a significant increase of extracellular vesicles (EVs). Treatment with GW4869, a specific inhibitor of neutral sphingomyelinase-2, decreased EV levels, suppressed ZIKV propagation, and reduced the release of infectious virions in astrocytes. Therefore, ZIKV infects primary human fetal astrocytes and the infection can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869. Further investigation into sphingomyelin metabolism and EVs may provide insights to the therapeutic treatment of ZIKV infection.

  3. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

    PubMed

    Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. Copyright © 2016 International Society

  4. Risk factors for nonreassuring fetal heart rate tracings after artificial rupture of membranes in spontaneous labor.

    PubMed

    Ganer Herman, Hadas; Tamayev, Liliya; Houli, Rotem; Miremberg, Hadas; Bar, Jacob; Kovo, Michal

    2018-04-24

    We aimed to characterize factors associated with nonreassuring fetal heart (FHR) tracings after artificial rupture of membranes (AROM), during the active phase of labor. Delivery charts of patients who presented in spontaneous labor, at term, between 2015 and 2016 were reviewed. We identified cases in which AROM was performed during the active stage of labor. We compared deliveries with a normal FHR and those who developed nonreassuring FHR. Nonreassuring FHR was defined as fetal tracing that necessitated intrauterine resuscitation, which included: oxytocin withheld, amnioinfusion, or immediate instrumental or cesarean birth. Of 664 deliveries, nonreassuring FHR occurred in 141 (21.2%) and normal FHR in 523 (78.7%). Both groups were notable for similar maternal characteristics and a similar gestational age. Epidural block was significantly more common in the nonreassuring FHR group (P < .001), as was meconium during delivery (P = .01). Deliveries in the nonreassuring FHR group were characterized by significantly lower Bishop scores at AROM. Mean birthweight was significantly lower in the nonreassuring FHR group (3201 ± 418 vs 3342 ± 376 g, P < .001), yet, neonatal outcome did not differ between the groups. In a multivariate logistic regression model, nulliparity, AROM at a station lower than -2, and increased birthweight were all significantly associated with a decreased rate of nonreassuring FHR, while prolonged duration from AROM to delivery and oxytocin augmentation significantly increased the risk for nonreassuring FHR. Nonreassuring FHR after AROM during delivery is associated with parity, fetal station at AROM, birthweight, and oxytocin augmentation. © 2018 Wiley Periodicals, Inc.

  5. Unexpected fetal death during pregnancy--a problem of unrecognized fetal disorders during antenatal care?

    PubMed

    Künzel, Wolfgang; Misselwitz, Björn

    2003-09-22

    To investigate the causes of ante partum fetal death (APFD) and to evaluate the diagnostic methods for prevention. A population-based retrospective study was conducted in 293091 deliveries from 1996 to 2000 in the State of Hesse, Germany. The investigations focus on mortality of infants during pregnancy, separated between singletons of 37-42 weeks (n=361) and 23-36 weeks (n=550), and multiple births (n=76). In 44 cases, the gestational age was unknown and in 19 cases lower than 23 weeks or greater than 43 weeks. In total 1006 cases remained and were subject for evaluation. Perinatal mortality (PM) was 0.56%. APFD occurred in 1050 cases (0.3%), i.e. 63.5% of PM. Risk factors from the medical history during pregnancy could be identified in 515 cases (51.2%). Significant risk factors were social burden (odds ratio (OR) 58.3), diabetes mellitus (OR 5.4) and gestational diabetes (OR 2.1), psychological burden (OR 4.8), proteinuria (OR 2.8), maternal age (OR 1.7) and maternal smoking, depending on the number of cigarettes. The risk factors show a difference in significance, if related to the gestational age and multiple pregnancies. The contribution of malformations to APFD was 7.8%. There was however a number of unexpected fetal deaths with unidentified risk factors: n=415 (41.3%). In this group, fetal growth restriction was observed in 38.1%. Compared to control, APFD was three to five times higher in fetal growth retardation below the 10th percentile. Fetal death was closely related to fetal surveillance, i.e. the number of antenatal visits, ultrasound measurements, and fetal heart rate monitoring. Fetal ante partum fetal death can be reduced at least by 50%, if the available methods for fetal surveillance are employed aiming to detect indications of fetal oxygen deprivation at an early stage.

  6. Computed tomographic imaging interpretation improves fetal outcomes after maternal trauma.

    PubMed

    Kopelman, Tammy R; Bogert, James N; Walters, Jarvis W; Gridley, Daniel; Guzman, Oscar; Davis, Karole M; Pieri, Paola G; Vail, Sydney J; Pressman, Melissa

    2016-12-01

    Computed tomography (CT) has been validated to identify and classify placental abruption following blunt trauma. The purpose of this study was to demonstrate improvement in fetal survival when delivery occurs by protocol at the first sign of class III fetal heart rate tracing in pregnant trauma patients with a viable fetus on arrival and CT evidence of placental perfusion 50% or less secondary to placental abruption. This is a retrospective review of pregnant trauma patients at 26 weeks' gestation or greater who underwent abdominopelvic CT as part of their initial evaluation. Charts were reviewed for CT interpretation of placental pathology with classification of placental abruption based upon enhancement (Grade 1, >50% perfusion; Grade 2, 25%-50% perfusion; Grade 3, <25% perfusion), as well as need for delivery and fetal outcomes. Forty-one patients met inclusion criteria. Computed tomography revealed evidence of placental abruption in six patients (15%): Grade 1, one patient, Grade 2, one patient, and Grade 3, four patients. Gestational ages ranged from 26 to 39 weeks. All patients with placental abruption of Grade 2 or greater developed concerning fetal heart tracings and underwent delivery emergently at first sign. Abruption was confirmed intraoperatively in all cases. Each birth was viable, and Apgar scores at 10 minutes were greater than 7 in 80% of infants, all of whom were ultimately discharged home. The remaining infant was transferred to an outside facility. Delivery at first sign of nonreassuring fetal heart rate tracings in pregnant trauma patients (third trimester) with placental abruption of Grade 2 or greater can lead to improved fetal outcome. Therapeutic/care management study, level III.

  7. GDNF and NGF family members and receptors in human fetal and adult spinal cord and dorsal root ganglia.

    PubMed

    Josephson, A; Widenfalk, J; Trifunovski, A; Widmer, H R; Olson, L; Spenger, C

    2001-11-12

    We describe the expression of mRNA encoding ligands and receptors of members of the GDNF family and members of the neurotrophin family in the adult human spinal cord and dorsal root ganglia (DRG). Fetal human spinal cord and ganglia were investigated for the presence of ligands and receptors of the neurotrophin family. Tissues were collected from human organ donors and after routine elective abortions. Messenger RNA was found encoding RET, GFR alpha-1, BDNF, trkB, and trkC in the adult human spinal cord and BDNF, NT-3, p75, trkB, and trkC in the fetal human spinal cord. The percentage of adult human DRG cells expressing p75, trkA, trkB, or trkC was 57, 46, 29, and 24%, respectively, and that of DRG cells expressing RET, GFR alpha-1, GFR alpha-2, or GFR alpha-3 was 79, 20, 51, and 32%, respectively. GFR alpha-2 was expressed selectively in small, GFR alpha-3 principally in small and GFR alpha-1 and RET in both large and small adult human DRG neurons. p75 and trkB were expressed by a wide range of DRG neurons while trkA was expressed in most small diameter and trkC primarily in large DRG neurons. Fetal DRG cells were positive for the same probes as adult DRG cells except for NT-3, which was only found in fetal DRG cells. Messenger RNA species only expressed at detectable levels in fetal but not adult spinal cord tissues included GDNF, GFR alpha-2, NT-3, and p75. Notably, GFR alpha-2, which is expressed in the adult rat spinal cord, was not found in the adult human spinal cord. Copyright 2001 Wiley-Liss, Inc.

  8. Myocardial strain abnormalities in fetal congenital heart disease assessed by speckle tracking echocardiography.

    PubMed

    Germanakis, Ioannis; Matsui, Hikoro; Gardiner, Helena M

    2012-01-01

    To compare myocardial deformation patterns in fetuses with congenital heart disease (CHD) with our reference range using speckle tracking echocardiography. We prospectively stored and analyzed 4-chamber loops of 28 fetuses with CHD (median gestation 27 weeks, range 20.9-37.0). The peak longitudinal left (LVs) and right (RVs) ventricular free wall Lagrangian strain and LV/RV strain ratio were measured from Syngo VVI software- (Siemens) derived original coordinates. Strain values from the first examination were compared with normative data from the same population using ANOVA with post hoc tests and serial examinations described in 14 fetuses. Simple shunt lesions (0.82) and shunts with pulmonary stenosis or atresia (0.93) had reduced mean LV/RV strain ratios compared to normal fetuses (1.01; 95% CI 0.97-1.05). Fetuses with hypoplastic left heart had the lowest (0.29), and those with Ebstein the highest (1.55), LV:RV ratio. Serial measurements showed increased LVs in aortic coarctation and aortic stenosis, but not in one developing important mitral regurgitation. Increased right ventricular loading in a fetus developing pulmonary regurgitation was associated with increasing RVs. Myocardial strain reflects the changing physiology of fetal CHD. Speckle tracking might be a useful tool to study the progress of myocardial function in affected fetuses. Copyright © 2012 S. Karger AG, Basel.

  9. Induced pluripotent stem (iPS) cells from human fetal stem cells.

    PubMed

    Guillot, Pascale V

    2016-02-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Fetal electrocardiograph

    NASA Astrophysics Data System (ADS)

    Rios, Heriberto; Andrade, Armando; Puente, Ernestina; Lizana, Pablo R.; Mendoza, Diego

    2002-11-01

    The high intra-uterine death rate is due to failure in appropriately diagnosing some problems in the cardiobreathing system of the fetus during pregnancy. The electrocardiograph is one apparatus which might detect problems at an early stage. With electrodes located near the womb and uterus, in a way similar to the normal technique, the detection of so-called biopotential differences, caused by concentrations of ions, can be achieved. The fetal electrocardiograph is based on an ultrasound technique aimed at detecting intrauterine problems in pregnant women, because it is a noninvasive technique due to the very low level of ultrasound power used. With this system, the following tests can be done: Heart movements from the ninth week onwards; Rapid and safe diagnosis of intrauterine fetal death; Location and size of the placenta. The construction of the fetal electrocardiograph requires instrument level components directly mounted on the printed circuit board, in order to avoid stray capacitance in the cabling which prevents the detection of the E.C.G. activity. The low cost of the system makes it affordable to low budget institutions; in contrast, available commercial systems are priced in U.S. Dollars. (To be presented in Spanish.)

  11. Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term.

    PubMed

    Frasch, Martin G; Keen, Ashley E; Gagnon, Robert; Ross, Michael G; Richardson, Bryan S

    2011-01-01

    Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23 ± 2 Hz from 3 ± 1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001). The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring.

  12. Monitoring Fetal Electrocortical Activity during Labour for Predicting Worsening Acidemia: A Prospective Study in the Ovine Fetus Near Term

    PubMed Central

    Frasch, Martin G.; Keen, Ashley E.; Gagnon, Robert; Ross, Michael G.; Richardson, Bryan S.

    2011-01-01

    Background Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Methodology/Principal Findings Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24±0.04, 52±13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23±2 Hz from 3±1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001). Conclusions/Significance The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such “adaptive brain shutdown,” the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring. PMID:21789218

  13. Four-dimensional ultrasonography of the fetal heart using color Doppler spatiotemporal image correlation.

    PubMed

    Gonçalves, Luís F; Romero, Roberto; Espinoza, Jimmy; Lee, Wesley; Treadwell, Marjorie; Chintala, Kavitha; Brandl, Helmut; Chaiworapongsa, Tinnakorn

    2004-04-01

    To describe clinical and research applications of 4-dimensional imaging of the fetal heart using color Doppler spatiotemporal image correlation. Forty-four volume data sets were acquired by color Doppler spatiotemporal image correlation. Seven subjects were examined: 4 fetuses without abnormalities, 1 fetus with ventriculomegaly and a hypoplastic cerebellum but normal cardiac anatomy, and 2 fetuses with cardiac anomalies detected by fetal echocardiography (1 case of a ventricular septal defect associated with trisomy 21 and 1 case of a double-inlet right ventricle with a 46,XX karyotype). The median gestational age at the time of examination was 21 3/7 weeks (range, 19 5/7-34 0/7 weeks). Volume data sets were reviewed offline by multiplanar display and volume-rendering methods. Representative images and online video clips illustrating the diagnostic potential of this technology are presented. Color Doppler spatiotemporal image correlation allowed multiplanar visualization of ventricular septal defects, multiplanar display and volume rendering of tricuspid regurgitation, volume rendering of the outflow tracts by color and power Doppler ultrasonography (both in a normal case and in a case of a double-inlet right ventricle with a double-outlet right ventricle), and visualization of venous streams at the level of the foramen ovale. Color Doppler spatiotemporal image correlation has the potential to simplify visualization of the outflow tracts and improve the evaluation of the location and extent of ventricular septal defects. Other applications include 3-dimensional evaluation of regurgitation jets and venous streams at the level of the foramen ovale.

  14. Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

    PubMed

    Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

    2011-04-01

    Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2-1-kHz pulse-repetition rate and 10-16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  15. Doppler ultrasonographic assessment of maternal and fetal arteries during normal feline gestation.

    PubMed

    Blanco, P G; Rodríguez, R; Olguín, S; Rube, A; Tórtora, M; Gobello, C

    2014-04-01

    The aim of this study was to describe Doppler parameters of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries, as well as fetal heart rate (FHR), during normal feline gestation. Fifteen, 1-4 years of age, weighing 2.5-3.9kg, domestic short-hair pregnant queens, which were born in our institutional cat colony were included in this study. Color and pulsed-wave Doppler evaluations of uterine arteries were performed every 10 days (Day 0, 10, 20, 30, 40, 50, 60) from mating. Fetal Doppler and M-mode ultrasonography were performed to assess umbilical, fetal abdominal aorta, fetal renal, fetal internal carotid arteries and FHR. Both peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine artery increased up to parturition (P<0.01), while resistance index (RI) decreased from Day 10 onwards (P<0.01). From Day 40 onwards, RI of umbilical artery diminished, while PSV and EDV augmented (P<0.01). Fetal abdominal aorta (P<0.01), renal (P<0.01) and internal carotid (P<0.01) arteries diminished their RI from Days 40, 60 and 40 onwards, respectively. Both PSV and EDV of these three arteries increased progressively. Fetal heart rate was first registered on Day 20 when it began to increase up to Day 40 and then diminished to the end of gestation (P<0.01). It is concluded that blood flow of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries progressively increased during normal feline pregnancy, while FHR rose to mid gestation and then decreased up to parturition. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Cellular and Molecular Effect of MEHP Involving LXRα in Human Fetal Testis and Ovary

    PubMed Central

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N’Tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Background Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Methodology/Principal Findings Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10−4M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. Conclusions/Significance We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells. PMID:23118965

  17. Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

    PubMed

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N'tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

  18. Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

    PubMed Central

    Gaudriault, Pierre; Mazaud-Guittot, Séverine; Lavoué, Vincent; Coiffec, Isabelle; Lesné, Laurianne; Dejucq-Rainsford, Nathalie; Scholze, Martin; Kortenkamp, Andreas

    2017-01-01

    Background: Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. Objectives: Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals. Methods: We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures. Results: We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight. Conclusions: Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014 PMID:28796631

  19. Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants.

    PubMed

    Gaudriault, Pierre; Mazaud-Guittot, Séverine; Lavoué, Vincent; Coiffec, Isabelle; Lesné, Laurianne; Dejucq-Rainsford, Nathalie; Scholze, Martin; Kortenkamp, Andreas; Jégou, Bernard

    2017-08-04

    Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals. We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures. We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight. Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014.

  20. The ovine fetal endocrine reflex responses to haemorrhage are not mediated by cardiac nerves

    PubMed Central

    Wood, Charles E

    2002-01-01

    This study was designed to test the hypothesis that cardiac receptors tonically inhibit the secretion of renin, arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) in late-gestation fetal sheep. Eight chronically catheterised fetal sheep between 122 and 134 days gestation were subjected to injection or infusion of saline or 4 % procaine into the pericardial space. Fetal blood pressure and heart rate were monitored and fetal blood samples were drawn to measure the response to these injections. Injection of procaine into the pericardial space effectively blocked cardiac nerves, as evidenced by a reduction in the variability of fetal heart rate and by the blockade of reflex reductions in fetal heart rate after intravenous injection of phenylephrine (an α-adrenergic agonist which raises blood pressure). Injection of saline had no discernable effects on any of the measured variables. A single injection of procaine, followed by a slow infusion, produced a transient blockade of cardiac nerves. Multiple injections of procaine produced a sustained blockade of cardiac nerves and a sustained rise in fetal plasma renin activity and ACTH. In none of the experiments did procaine significantly alter fetal plasma AVP concentrations. In 11 fetuses between 121 and 134 days gestation, we combined the cardiac nerve blockade with slow haemorrhage to test the cardiac nerves as mediators of the endocrine response to haemorrhage in utero. Cardiac nerve blockade exaggerated the fetal blood gas response to haemorrhage somewhat but did not significantly alter the magnitude of the ACTH, AVP, or plasma renin activity response to haemorrhage. We conclude that cardiac nerves in the late-gestation fetal sheep have minor influences on plasma renin activity and ACTH in normovolaemic fetuses, but that changes in cardiac nerve activity do not mediate the endocrine responsiveness to haemorrhage. PMID:12042365

  1. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts

    PubMed Central

    Chong, James J.H.; Yang, Xiulan; Don, Creighton W.; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M.; Van Biber, Benjamin; Cook, Savannah M.; Palpant, Nathan J; Gantz, Jay; Fugate, James A.; Muskheli, Veronica; Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A.; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.

    2014-01-01

    Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure 1 by providing human cardiomyocytes to support heart regeneration 2. Studies of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in small animal models have shown favorable effects of this treatment 3–7. It remains unknown, however, whether clinical scale hESC-CMs transplantation is feasible, safe or can provide large-scale myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (>1 billion cells/batch) and cryopreserved with good viability. Using a non-human primate (NHP) model of myocardial ischemia-reperfusion, we show that that cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs generates significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a three-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small animal models 7, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome. PMID:24776797

  2. Comparison of data mining techniques applied to fetal heart rate parameters for the early identification of IUGR fetuses.

    PubMed

    Magenes, G; Bellazzi, R; Malovini, A; Signorini, M G

    2016-08-01

    The onset of fetal pathologies can be screened during pregnancy by means of Fetal Heart Rate (FHR) monitoring and analysis. Noticeable advances in understanding FHR variations were obtained in the last twenty years, thanks to the introduction of quantitative indices extracted from the FHR signal. This study searches for discriminating Normal and Intra Uterine Growth Restricted (IUGR) fetuses by applying data mining techniques to FHR parameters, obtained from recordings in a population of 122 fetuses (61 healthy and 61 IUGRs), through standard CTG non-stress test. We computed N=12 indices (N=4 related to time domain FHR analysis, N=4 to frequency domain and N=4 to non-linear analysis) and normalized them with respect to the gestational week. We compared, through a 10-fold crossvalidation procedure, 15 data mining techniques in order to select the more reliable approach for identifying IUGR fetuses. The results of this comparison highlight that two techniques (Random Forest and Logistic Regression) show the best classification accuracy and that both outperform the best single parameter in terms of mean AUROC on the test sets.

  3. Support-vector-machines-based multidimensional signal classification for fetal activity characterization

    NASA Astrophysics Data System (ADS)

    Ribes, S.; Voicu, I.; Girault, J. M.; Fournier, M.; Perrotin, F.; Tranquart, F.; Kouamé, D.

    2011-03-01

    Electronic fetal monitoring may be required during the whole pregnancy to closely monitor specific fetal and maternal disorders. Currently used methods suffer from many limitations and are not sufficient to evaluate fetal asphyxia. Fetal activity parameters such as movements, heart rate and associated parameters are essential indicators of the fetus well being, and no current device gives a simultaneous and sufficient estimation of all these parameters to evaluate the fetus well-being. We built for this purpose, a multi-transducer-multi-gate Doppler system and developed dedicated signal processing techniques for fetal activity parameter extraction in order to investigate fetus's asphyxia or well-being through fetal activity parameters. To reach this goal, this paper shows preliminary feasibility of separating normal and compromised fetuses using our system. To do so, data set consisting of two groups of fetal signals (normal and compromised) has been established and provided by physicians. From estimated parameters an instantaneous Manning-like score, referred to as ultrasonic score was introduced and was used together with movements, heart rate and associated parameters in a classification process using Support Vector Machines (SVM) method. The influence of the fetal activity parameters and the performance of the SVM were evaluated using the computation of sensibility, specificity, percentage of support vectors and total classification accuracy. We showed our ability to separate the data into two sets : normal fetuses and compromised fetuses and obtained an excellent matching with the clinical classification performed by physician.

  4. Biomedical Instruments for Fetal and Neonatal Surveillance

    NASA Astrophysics Data System (ADS)

    Rolfe, P.; Scopesi, F.; Serra, G.

    2006-10-01

    Specialised instruments have been developed to aid the care of the fetus and the newborn baby. Miniature sensors using optical, electrical, chemical, mechanical and magnetic principles have been produced for capturing key measurands. These include temperature, pressure, flow and dimension, as well as several specific molecules such as glucose, oxygen and carbon dioxide. During pregnancy ultrasound imaging and blood flow techniques provide valuable information concerning fetal abnormalities, fetal growth, fetal breathing and fetal heart rate. Signal processing and pattern recognition can be useful for deriving indicators of fetal distress and clinical status, based on biopotentials as well as ultrasound signals. Fetal pH measurement is a critical requirement during labour and delivery. The intensive care of ill preterm babies involves provision of an optimal thermal environment and respiratory support. Monitoring of blood gas and acid-base status is essential, and this involves both blood sampling for in vitro analysis as well as the use of invasive or non-invasive sensors. For the future it will be vital that the technologies used are subjected to controlled trials to establish benefit or otherwise.

  5. Nitric oxide synthase mRNA expression in human fetal membranes: a possible role in parturition.

    PubMed

    Dennes, W J; Slater, D M; Bennett, P R

    1997-04-07

    Nitric oxide (NO) is a potent endogenous smooth-muscle relaxant. It is synthesised from 1-arginine by isoforms of nitric oxide synthase (NOS). Whilst it is clear that the uterus responds to NO by relaxation, NOS expression has not been investigated in fetal membranes or myometrium in human pregnancy. This study has shown, using semi-quantitative RT-PCR, expression of cNOS mRNA in human amnion, chorion-decidua, and placenta. iNOS mRNA expression was demonstrated in human amnion, chorion-decidua, and placenta. It is possible that NO synthesised in fetal membranes may act either directly to inhibit myometrial contractility or indirectly to interact with other labour-associated genes, such as cyclo-oxygenase, to coordinate the onset of labour.

  6. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    PubMed

    Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

    2013-01-01

    -Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy.

  7. Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study

    PubMed Central

    Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M.; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E.; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P.

    2013-01-01

    -Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy. PMID:23533575

  8. Transplantation of human fetal tissue for neurodegenerative diseases: validation of a new protocol for microbiological analysis and bacterial decontamination.

    PubMed

    Piroth, Tobias; Pauly, Marie-Christin; Schneider, Christian; Wittmer, Annette; Möllers, Sven; Döbrössy, Máté; Winkler, Christian; Nikkhah, Guido

    2014-01-01

    Restorative cell therapy concepts in neurodegenerative diseases are aimed at replacing lost neurons. Despite advances in research on pluripotent stem cells, fetal tissue from routine elective abortions is still regarded as the only safe cell source. Progenitor cells isolated from distinct first-trimester fetal CNS regions have already been used in clinical trials and will be used again in a new multicenter trial funded by the European Union (TRANSEURO). Bacterial contamination of human fetal tissue poses a potential risk of causing infections in the brain of the recipient. Thus, effective methods of microbial decontamination and validation of these methods are required prior to approval of a neurorestorative cell therapy trial. We have developed a protocol consisting of subsequent washing steps at different stages of tissue processing. Efficacy of microbial decontamination was assessed on rat embryonic tissue incubated with high concentrations of defined microbe solutions including representative bacterial and fungal species. Experimental microbial contamination was reduced by several log ranks. Subsequently, we have analyzed the spectrum of microbial contamination and the effect of subsequent washing steps on aborted human fetal tissue; 47.7% of the samples taken during human fetal tissue processing were positive for a microbial contamination, but after washing, no sample exhibited bacterial growth. Our data suggest that human fetal tissue for neural repair can carry microbes of various species, highlighting the need for decontamination procedures. The decontamination protocol described in this report has been shown to be effective as no microbes could be detected at the end of the procedure.

  9. Morphology and biomechanics of human heart

    NASA Astrophysics Data System (ADS)

    Chelnokova, Natalia O.; Golyadkina, Anastasiya A.; Kirillova, Irina V.; Polienko, Asel V.; Ivanov, Dmitry V.

    2016-03-01

    Object of study: A study of the biomechanical characteristics of the human heart ventricles was performed. 80 hearts were extracted during autopsy of 80 corpses of adults (40 women and 40 men) aged 31-70 years. The samples were investigated in compliance with the recommendations of the ethics committee. Methods: Tension and compression tests were performed with help of the uniaxial testing machine Instron 5944. Cardiometry was also performed. Results: In this work, techniques for human heart ventricle wall biomechanical properties estimation were developed. Regularities of age and gender variability in deformative and strength properties of the right and left ventricle walls were found. These properties were characterized by a smooth growth of myocardial tissue stiffness and resistivity at a relatively low strain against reduction in their strength and elasticity from 31-40 to 61-70 years. It was found that tissue of the left ventricle at 61-70 years had a lower stretchability and strength compared with tissues of the right ventricle and septum. These data expands understanding of the morphological organization of the heart ventricles, which is very important for the development of personalized medicine. Taking into account individual, age and gender differences of the heart ventricle tissue biomechanical characteristics allows to rationally choosing the type of patching materials during reconstructive operations on heart.

  10. Validation of a computerized algorithm to quantify fetal heart rate deceleration area.

    PubMed

    Gyllencreutz, Erika; Lu, Ke; Lindecrantz, Kaj; Lindqvist, Pelle G; Nordstrom, Lennart; Holzmann, Malin; Abtahi, Farhad

    2018-05-16

    Reliability in visual cardiotocography interpretation is unsatisfying, which has led to development of computerized cardiotocography. Computerized analysis is well established for antenatal fetal surveillance, but has yet not performed sufficiently during labor. We aimed to investigate the capacity of a new computerized algorithm compared to visual assessment in identifying intrapartum fetal heart rate baseline and decelerations. Three-hundred-and-twelve intrapartum cardiotocography tracings with variable decelerations were analysed by the computerized algorithm and visually examined by two observers, blinded to each other and the computer analysis. The width, depth and area of each deceleration was measured. Four cases (>100 variable decelerations) were subject to in-depth detailed analysis. The outcome measures were bias in seconds (width), beats per minute (depth), and beats (area) between computer and observers by using Bland-Altman analysis. Interobserver reliability was determined by calculating intraclass correlation and Spearman rank analysis. The analysis (312 cases) showed excellent intraclass correlation (0.89-0.95) and very strong Spearman correlation (0.82-0.91). The detailed analysis of > 100 decelerations in 4 cases revealed low bias between the computer and the two observers; width 1.4 and 1.4 seconds, depth 5.1 and 0.7 beats per minute, and area 0.1 and -1.7 beats. This was comparable to the bias between the two observers; 0.3 seconds (width), 4.4 beats per minute (depth), and 1.7 beats (area). The intraclass correlation was excellent (0.90-0.98). A novel computerized algorithm for intrapartum cardiotocography analysis is as accurate as gold standard visual assessment with high correlation and low bias. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta

    PubMed Central

    Sardesai, Varda S.; Shafiee, Abbas; Fisk, Nicholas M.

    2017-01-01

    Abstract Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender‐discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi‐derived MSC (CV‐MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV‐MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070–1084 PMID:28205414

  12. Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease.

    PubMed

    Ruiz, A; Cruz-Lemini, M; Masoller, N; Sanz-Cortés, M; Ferrer, Q; Ribera, I; Martínez, J M; Crispi, F; Arévalo, S; Gómez, O; Pérez-Hoyos, S; Carreras, E; Gratacós, E; Llurba, E

    2017-03-01

    To determine the longitudinal behavior of fetal biometric measures and cerebroplacental hemodynamics throughout gestation in fetuses with congenital heart disease (CHD). Fetal biometry and Doppler hemodynamics (uterine artery (UtA), umbilical artery (UA) and fetal middle cerebral artery (MCA)) were measured serially in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (20-25 weeks) to delivery, with at least two measurements per fetus that were at least 2 weeks apart. Fetuses were classified into three groups according to the pattern of blood supply to the brain (placental vs systemic) that would be expected on the basis of the type of CHD. All parameters were transformed into Z-scores. A linear mixed model to analyze repeated measurements was constructed for each parameter to assess its behavior throughout gestation. Four hundred and forty-four ultrasound examinations were performed in 119 CHD fetuses, with a median of two measurements per fetus. The fetuses presented a small head at diagnosis (biparietal diameter (BPD) Z-score, -1.32 ± 0.99; head circumference (HC) Z-score, -0.79 ± 1.02), which remained small throughout gestation. UtA and UA pulsatility indices (PI) showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA-PI or cerebroplacental ratio (CPR) with gestational age. Both MCA and CPR presented significant differences in longitudinal behavior between CHD groups, while BPD and HC did not. CHD fetuses have a relatively small head from the second trimester of pregnancy, regardless of the type of CHD anomaly, and increasing resistance in the UtA and UA as pregnancy progresses, suggestive of increasing degree of placental impairment. Our findings indicate the early onset of mechanisms that could lead to poorer neurodevelopment later in life. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by

  13. Genome-wide analysis of alternative splicing during human heart development

    NASA Astrophysics Data System (ADS)

    Wang, He; Chen, Yanmei; Li, Xinzhong; Chen, Guojun; Zhong, Lintao; Chen, Gangbing; Liao, Yulin; Liao, Wangjun; Bin, Jianping

    2016-10-01

    Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.

  14. Embryologic and Fetal Development of the Human Eyelid

    PubMed Central

    Abdulhafez, Mohamed H.; Fouad, Yousef A.; Dutton, Jonathan J.

    2016-01-01

    Purpose: To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life. Methods: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis. Results: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession. Conclusions: Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies. PMID:27124372

  15. Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial.

    PubMed

    2017-04-29

    Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes. In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks' gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152. Between Jan 6, 2010, and Aug 31, 2013, 47 062 women were randomly assigned (23 515 in the decision-support group and 23 547 in the no-decision-support group) and 46 042 were analysed (22 987 in the decision-support group and 23 055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups-172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82-1·25). At 2 years, no significant differences were noted in terms of developmental assessment. Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal

  16. Fetal Electrocardiogram Extraction and Analysis Using Adaptive Noise Cancellation and Wavelet Transformation Techniques.

    PubMed

    Sutha, P; Jayanthi, V E

    2017-12-08

    Birth defect-related demise is mainly due to congenital heart defects. In the earlier stage of pregnancy, fetus problem can be identified by finding information about the fetus to avoid stillbirths. The gold standard used to monitor the health status of the fetus is by Cardiotachography(CTG), cannot be used for long durations and continuous monitoring. There is a need for continuous and long duration monitoring of fetal ECG signals to study the progressive health status of the fetus using portable devices. The non-invasive method of electrocardiogram recording is one of the best method used to diagnose fetal cardiac problem rather than the invasive methods.The monitoring of the fECG requires development of a miniaturized hardware and a efficient signal processing algorithms to extract the fECG embedded in the mother ECG. The paper discusses a prototype hardware developed to monitor and record the raw mother ECG signal containing the fECG and a signal processing algorithm to extract the fetal Electro Cardiogram signal. We have proposed two methods of signal processing, first is based on the Least Mean Square (LMS) Adaptive Noise Cancellation technique and the other method is based on the Wavelet Transformation technique. A prototype hardware was designed and developed to acquire the raw ECG signal containing the mother and fetal ECG and the signal processing techniques were used to eliminate the noises and extract the fetal ECG and the fetal Heart Rate Variability was studied. Both the methods were evaluated with the signal acquired from a fetal ECG simulator, from the Physionet database and that acquired from the subject. Both the methods are evaluated by finding heart rate and its variability, amplitude spectrum and mean value of extracted fetal ECG. Also the accuracy, sensitivity and positive predictive value are also determined for fetal QRS detection technique. In this paper adaptive filtering technique uses Sign-sign LMS algorithm and wavelet techniques with

  17. Fetal growth: a review of terms, concepts and issues relevant to obstetrics.

    PubMed

    Mayer, C; Joseph, K S

    2013-02-01

    The perinatal literature includes several potentially confusing and controversial terms and concepts related to fetal size and growth. This article discusses fetal growth from an obstetric perspective and addresses various issues including the physiologic mechanisms that determine fetal growth trajectories, known risk factors for abnormal fetal growth, diagnostic and prognostic issues related to restricted and excessive growth and temporal trends in fetal growth. Also addressed are distinctions between fetal growth 'standards' and fetal growth 'references', and between fetal growth charts based on estimated fetal weight vs those based on birth weight. Other concepts discussed include the incidence of fetal growth restriction in pregnancy (does the frequency of fetal growth restriction increase or decrease with increasing gestation?), the obstetric implications of studies showing associations between fetal growth and adult chronic illnesses (such as coronary heart disease) and the need for customizing fetal growth standards. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

  18. Neonatal Arterial Morphology Is Related to Body Size in Abnormal Human Fetal Growth.

    PubMed

    Olander, Rasmus F W; Sundholm, Johnny K M; Ojala, Tiina H; Andersson, Sture; Sarkola, Taisto

    2016-09-01

    Restriction in fetal growth is associated with cardiovascular disease in adulthood. It is unclear whether abnormal intrauterine growth influences arterial morphology during the fetal or neonatal stage. The objective was to study the regional arterial morphology with respect to gestational age and abnormal fetal body size. We studied body anthropometrics and arterial morphology and physiology in 174 neonates born between 31 and 42 weeks of gestation, including neonates with birth weights appropriate, small, and large for age, with very high resolution vascular ultrasound (35-55 MHz). In simple linear regressions, parameters of body size (body weight, body surface area, and organ circumference) and gestational age were statistically significantly associated with common carotid, brachial, femoral arterial parameters (lumen diameter [LD], wall layer thickness [intima-media thickness and intima-media-adventitia thickness], and carotid artery wall stress [CAWS]). Male sex was statistically significantly associated with LD and CAWS. In multiple linear regression models, body size, gestational age, and sex explained a large proportion of the arterial variance (R( 2) range, 0.37-0.47 for LD; 0.09-0.35 for intima-media thickness; 0.21-0.41 for intima-media-adventitia thickness; and 0.23 for CAWS; all models P<0.001). Arterial wall layer thickness, LDs, and CAWS were independently and strongly predicted by body size, and no effect of maternal disease was observed when added to the models. Gestational age and male sex were also independently but more weakly associated with arterial LDs and CAWS (P<0.01), but not with arterial wall layers. These results indicate that the intrauterine growth of fetal arterial LD and wall layer thickness are primarily attributed to body growth overall. LD and CAWS show weaker association with gestational age and sex. © 2016 American Heart Association, Inc.

  19. Cardiovascular cast model fabrication and casting effectiveness evaluation in fetus with severe congenital heart disease or normal heart.

    PubMed

    Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng

    2016-04-01

    To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.

  20. Killing Me Softly: The Fetal Origins Hypothesis*

    PubMed Central

    Almond, Douglas

    2013-01-01

    In the epidemiological literature, the fetal origins hypothesis associated with David J. Barker posits that chronic, degenerative conditions of adult health, including heart disease and type 2 diabetes, may be triggered by circumstance decades earlier, in utero nutrition in particular. Economists have expanded on this hypothesis, investigating a broader range of fetal shocks and circumstances and have found a wealth of later-life impacts on outcomes including test scores, educational attainment, and income, along with health. In the process, they have provided some of the most credible observational evidence in support of the hypothesis. The magnitude of the impacts is generally large. Thus, the fetal origins hypothesis has not only survived contact with economics, but has flourished. PMID:25152565

  1. Fetal evaluation for transport by ultrasound performed by air medical teams: A case series.

    PubMed

    Polk, James D; Merlino, James I; Kovach, Betty L; Mancuso, Charlene; Fallon, William F

    2004-01-01

    The air medical team has limited options when evaluating the obstetrical patient and assessing fetal health during air transport to a high-risk obstetrical unit. Traditionally, physical examination and a Doppler stethoscope have been used to determine fetal heart rates and movement. However, with the advent of portable ultrasound technology, new information about the mother and child are available to the air medical crew. The Fetal Evaluation for Transport with Ultrasound (FETUS) is a screening examination that consists of an evaluation of the fetal heart rate, position, and movement and general condition of the placenta. The examination can be repeated in flight with no acoustic distortion from rotor noise. The additional information can be advantageous when transport decisions need to be made or when conditions do not allow Doppler stethoscope use.

  2. Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

    PubMed

    Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

    2018-04-01

    Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P<.05). A total of 609 probe sets were expressed differentially (>1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included

  3. ACE phenotyping in human heart.

    PubMed

    Tikhomirova, Victoria E; Kost, Olga A; Kryukova, Olga V; Golukhova, Elena Z; Bulaeva, Naida I; Zholbaeva, Aigerim Z; Bokeria, Leo A; Garcia, Joe G N; Danilov, Sergei M

    2017-01-01

    Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.

  4. ACE phenotyping in human heart

    PubMed Central

    Tikhomirova, Victoria E.; Kost, Olga A.; Kryukova, Olga V.; Golukhova, Elena Z.; Bulaeva, Naida I.; Zholbaeva, Aigerim Z.; Bokeria, Leo A.; Garcia, Joe G. N.

    2017-01-01

    Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10–15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk. PMID:28771512

  5. Partitioning of glutamine synthesised by the isolated perfused human placenta between the maternal and fetal circulations☆

    PubMed Central

    Day, P.E.L.; Cleal, J.K.; Lofthouse, E.M.; Goss, V.; Koster, G.; Postle, A.; Jackson, J.M.; Hanson, M.A.; Jackson, A.A.; Lewis, R.M.

    2013-01-01

    Introduction Placental glutamine synthesis has been demonstrated in animals and is thought to increase the availability of this metabolically important amino acid to the fetus. Glutamine is of fundamental importance for cellular replication, cellular function and inter-organ nitrogen transfer. The objective of this study was to investigate the role of glutamate/glutamine metabolism by the isolated perfused human placenta in the provision of glutamine to the fetus. Methods Glutamate metabolism was investigated in the isolated dually perfused human placental cotyledon. U–13C-glutamate was used to investigate the movement of carbon and 15N-leucine to study movement of amino-nitrogen. Labelled amino acids were perfused via maternal or fetal arteries at defined flow rates. The enrichment and concentration of amino acids in the maternal and fetal veins were measured following 5 h of perfusion. Results Glutamate taken up from the maternal and fetal circulations was primarily converted into glutamine the majority of which was released into the maternal circulation. The glutamine transporter SNAT5 was localised to the maternal-facing membrane of the syncytiotrophoblast. Enrichment of 13C or 15N glutamine in placental tissue was lower than in either the maternal or fetal circulation, suggesting metabolic compartmentalisation within the syncytiotrophoblast. Discussion Placental glutamine synthesis may help ensure the placenta's ability to supply this amino acid to the fetus does not become limiting to fetal growth. Glutamine synthesis may also influence placental transport of other amino acids, metabolism, nitrogen flux and cellular regulation. Conclusions Placental glutamine synthesis may therefore be a central mechanism in ensuring that the human fetus receives adequate nutrition and is able to maintain growth. PMID:24183194

  6. Ex vivo culture of human fetal gonads: manipulation of meiosis signalling by retinoic acid treatment disrupts testis development.

    PubMed

    Jørgensen, A; Nielsen, J E; Perlman, S; Lundvall, L; Mitchell, R T; Juul, A; Rajpert-De Meyts, E

    2015-10-01

    What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenotype in fetal testis cultures. One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA-treatment mediates initiation of meiosis in human fetal ovary ex vivo. This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated outcomes included tissue integrity and morphology, cell proliferation and survival and the expression of markers of meiosis and sex differentiation. Tissue from 24 first trimester human fetuses was included in this study, all from elective terminations at gestational week (GW) 7-12. Gonads were cultured for 2 weeks with and without addition of 1 µM RA. Samples were subsequently formalin-fixed and investigated by immunohistochemistry and cell counting. Proteins investigated and quantified included; octamer-binding transcription factor 4 (OCT4), transcription factor AP-2 gamma (AP2γ) (embryonic germ cell markers), SRY (sex determining region Y)-box 9 (SOX9), anti-Müllerian hormone (AMH) (immature Sertoli cell markers), COUP transcription factor 2 (COUP-TFII) (marker of interstitial cells), forkhead box L2 (FOXL2) (granulosa cell marker), H2A histone family, member X (γH2AX) (meiosis marker), doublesex and mab-3 related transcription factor 1 (DMRT1) (meiosis regulator), cleaved poly ADP ribose polymerase (PARP), cleaved Caspase 3 (apoptosis markers) and Ki-67 antigen (Ki-67) (proliferation marker). Also, proliferation was determined using a 5'-bromo-2

  7. Congenital Heart Defects and Measures of Fetal Growth in Newborns with Down Syndrome or 22q11.2 Deletion Syndrome.

    PubMed

    Matthiesen, Niels B; Agergaard, Peter; Henriksen, Tine B; Bach, Cathrine C; Gaynor, J William; Hjortdal, Vibeke; Østergaard, John R

    2016-08-01

    To estimate the association between congenital heart defects (CHD) and indices of fetal growth in Down and 22q11.2 deletion syndromes. We established 2 Danish nationwide cohorts of newborn singletons with either Down syndrome (n = 670) or 22q11.2 deletion syndrome (n = 155), born 1997-2011. In both cohorts, we analyzed the association between CHD, CHD severity, and indices of fetal growth by multivariable linear regression adjusted for potential confounders. We report mean differences in gestational age specific z-scores compared with newborns without CHD. Down syndrome and 22q11.2 deletion syndrome were both associated with lower mean birth weight and head circumference z-scores. We found no association between CHD or CHD severity and indices of fetal growth. In Down syndrome, the association between any CHD and the mean difference in head circumference z-score was 0.03 (95% CI -0.12, 0.18), and the estimate regarding birth weight z-score was 0.09 (95% CI -0.08, 0.25). The corresponding estimates in 22q11.2 deletion syndrome were 0.00 (95% CI -0.33, 0.32) and -0.09 (95% CI -0.45, 0.26). We found no association between CHD and fetal growth measures in newborns with Down syndrome or 22q11.2 deletion syndrome. Thus, in certain subtypes of CHD, the contribution of genetic factors to prenatal growth impairment may be more important than circulatory disturbances. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.

    PubMed

    Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W

    2013-06-01

    Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.

  9. Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

    PubMed

    Gepstein, Lior; Kehat, Izhak

    2005-02-01

    Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

  10. Feasibility of noninvasive fetal electrocardiographic monitoring in a clinical setting.

    PubMed

    Arya, Bhawna; Govindan, Rathinaswamy; Krishnan, Anita; Duplessis, Adre; Donofrio, Mary T

    2015-06-01

    Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting. The fECG device has the ability to acquire fECG signals and allow calculation of fetal cardiac time intervals between 16- and 42-week gestational age (GA). We aimed to demonstrate the feasibility of fECG acquisition in a busy fetal cardiology clinic using the Monica fetal heart rate monitor. This is a prospective observational pilot study of fECG acquired from fetuses referred for fetal echocardiography. Recordings were performed for 5-15 min. Maternal signals were attenuated and fECG averaged. fECG and fetal cardiac time intervals (PR, QRS, RR, and QT) were evaluated by two cardiologists independently and inter-observer reliability was assessed using intraclass coefficient (ICC). Sixty fECGs were collected from 50 mothers (mean GA 28.1 ± 6.1). Adequate signal-averaged waveforms were obtained in 20 studies with 259 cardiac cycles. Waveforms could not be obtained between 26 and 30 weeks. Fetal cardiac time intervals were measured and were reproducible for PR (ICC = 0.89; CI 0.77-0.94), QRS (ICC = 0.79; CI 0.51-0.91), and RR (ICC = 0.77; CI 0.53-0.88). QT ICC was poor due to suboptimal T-wave tracings. Acquisition of fECG and measurement of fetal cardiac time intervals is feasible in a clinical setting between 19- and 42-week GA, though tracings are difficult to obtain, especially between 26 and 30 weeks. There was high reliability in fetal cardiac time intervals measurements, except for QT. The device may be useful for assessing atrioventricular/intraventricular conduction in fetuses from 20 to 26 and >30 weeks. Techniques to improve signal acquisition, namely T-wave amplification, are ongoing.

  11. Fetal Liver Bisphenol A Concentrations and Biotransformation Gene Expression Reveal Variable Exposure and Altered Capacity for Metabolism in Humans

    PubMed Central

    Nahar, Muna S.; Liao, Chunyang; Kannan, Kurunthachalam; Dolinoy, Dana C.

    2013-01-01

    Widespread exposure to the endocrine active compound, bisphenol A (BPA), is well documented in humans. A growing body of literature suggests adverse health outcomes associated with varying ranges of exposure to BPA. In the current study, we measured the internal dose of free BPA and conjugated BPA and evaluated gene expression of bio-transformation enzymes specific for BPA metabolism in 50 first- and second-trimester human fetal liver samples. Both free BPA and conjugated BPA concentrations varied widely, with free BPA exhibiting three times higher concentrations than conjugated BPA concentrations. As compared to gender-matched adult liver controls, UDP-glucuronyltransferase, sulfotransferase, and steroid sulfatase genes exhibited reduced expression whereas β-glucuronidase mRNA expression remained unchanged in the fetal tissues. This study provides evidence that there is considerable exposure to BPA during human pregnancy and that the capacity for BPA metabolism is altered in the human fetal liver. PMID:23208979

  12. Maternal and fetal effects of chocolate consumption during pregnancy: a systematic review.

    PubMed

    Latif, Rabia

    2018-03-13

    The purpose of this review is to explore the effects of chocolate consumption during pregnancy on fetus and mother herself. Randomized controlled trials/quasi-experimental/observational/controlled before and after studies involving chocolate/cocoa/cacao consumption (irrespective of type or dose, composition, exposure period, and method of administration) among pregnant women/animals; and measuring any outcome (beneficial or harmful) related to fetus or mother after chocolate exposure were included. Databases searched were PubMed, Web of Science and Scopus; between April and May 2017. Risk of bias within each human randomized controlled trial (RCT) and animals' experimental studies was evaluated by "The Cochrane Collaboration's tool" and SYRCLE's tool respectively. Fourteen human studies including a total of 6639 participants and nine animal studies were selected. Outcome variables investigated in human studies were maternal blood pressure, fetal heart rate, and striae gravidarum. Animal studies explored chocolate-induced teratogenicity and fetal metabolic derangements. Ten out of these 23 studies reported chocolate to be "beneficial"; five studies reported adverse effects, whereas eight studies declared chocolate as "neutral". Maternal chocolate intake has acute stimulatory effects on fetal reactivity and chronic blood pressure reducing effect in mothers. Chocolate is nonteratogenic and does not affect reproductive indices. Metabolic derangements in offsprings born to chocolate fed dams have been reported. Pregnant females must be careful about consumption of cocoa and chocolate. Future studies should be planned, keeping in view heterogeneities identified across the selected studies in this review.

  13. Fetal anemia as a signal of congenital syphilis.

    PubMed

    Macé, Guillaume; Castaigne, Vanina; Trabbia, Aurore; Guigue, Virginie; Cynober, Evelyne; Cortey, Anne; Lalande, Valérie; Carbonne, Bruno

    2014-09-01

    An upsurge in syphilis has been observed almost everywhere over the past decade. The mother's clinical presentation is often uninformative. The diagnosis of maternal syphilis infection is most often based on serologic tests that allow early Extencilline treatment. Syphilis ultrasound findings are non-specific, and delay before treatment can be decisive for prognosis. Fetal anemia is a physiological consequence of severe infection. We confirmed that syphilis can be suggested non-invasively by MCA-PSV measurements in a context of ascitis or atypical hydrops in the absence of usual causes. It is therefore important to perform maternal TPHA/VDRL serology if fetal anemia is suspected. In association with Extencilline treatment, intra uterine transfusion can limit consequences of infection. Reduced fetal movements and non-reactive fetal heart rate may prefigure acute perinatal complications or stillbirth.

  14. [Fetal growth and activity at 20 to 24 weeks of gestation (preliminary study)].

    PubMed

    Conde, Ana; Figueiredo, Bárbara; Tendais, Iva; Pereira, Ana F; Afonso, Elisa; Nogueira, Raúl

    2008-01-01

    Recent researches show that psychological development begins much before birth and prenatal influences can explain a significant part of the future variability in infants' behaviour and development. The aim of this study was to characterize the fetal development between 20 and 24 weeks of gestation, related to the measures of fetal growth-- iparietal diameter, abdominal circumference, head circumference, femur length and fetal weight-- and fetal activity--fetal heart rate and fetal movements. We also tried to establish if there are any differences in these measures related to the mothers' and fetus' sociodemographic features, obstetrical conditions and exposure to drugs. The sample of this study involved 48 fetus (52.1% female and 47.9% male) with an estimated gestational age (GA) between 20-24 weeks (Mean = 21 weeks and 1 day), whose mothers had appointments at the Obstetric and Gynaecological medical consultation of Júlio Dinis Maternity Hospital (MJD, Oporto). A video tape of the fetal behaviour was made and ultrasound biometry measurements were collected from the morphological ultrasound report. A statistical analysis of fetal data, after gestational age control, showed differences in fetal growth measures related to mothers' occupational status [F(1,41) = 7.28; p = .000], marital status [F(1,41) = 2.61; p = .04], household arrangements [F(1,41) = 2.91; p = .03] and coffee consumption [F(1,40) = 2.55; p = .05]. Differences in fetal activity measures (fetal heart rate) associated to fetus gender [F(1,16) = 5.84; p = .009] were also found. We can conclude about the sensibility of fetal development to prenatal factors related to the mothers' and fetus' sociodemographic features and exposure to drugs.

  15. Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficiency on Fetal Oxygen Metabolism and Congenital Heart Defects

    DTIC Science & Technology

    2017-10-01

    equivalent to O2 in air at altitudes from 25,000-4,000 ft elevation. ODDluc activity is measures in the fetal tissues as an index of hypoxic stress ...inspired O2. This corresponds to elevations of 25,000-7000 feet. The hypoxic stress placed on the embryo organs (heart, liver, brain) in a normal pregnancy...embryo is particularly vulnerable to reductions in the supply of O2 coming from the mother. 3) The combined stress of placental insufficiency plus

  16. Therapeutic amnioinfusion for intrapartum fetal distress using a pediatric feeding tube.

    PubMed

    Abdel-Aleem, H; Amin, A F; Shokry, M; Radwan, R A

    2005-08-01

    To evaluate the role of therapeutic amnioinfusion using a pediatric feeding tube in cases of intrapartum fetal distress. A randomized clinical trial including 438 women admitted in labor at Assiut University Hospital with nonreassuring fetal heart rate tracing. Using sealed opaque envelopes, the women were randomized to 2 groups. In the amnioinfusion group they underwent transcervical amnioinfusion (1000 mL of warmed sterile saline solution) in addition to conventional treatment. In the control group they received conventional treatment only. The primary outcome was cesarean section rate for fetal distress. The secondary outcomes were neonatal and maternal complications. The amnioinfusion group showed a significant reduction in the rate of cesarean section for fetal distress (relative risk [RR], 0.7; 95% confidence interval [CI], 0.6-0.83), and a 30% reduction in abnormal fetal heart rate patterns (RR, 0.7; 95% CI, 0.6-0.83). Significantly fewer newborns had Apgar scores less than 7 at 1 and 5 min in the amnioinfusion group than in the control group (RR, 0.38; 95% CI, 0.26-0.55 and RR, 0.31; 95% CI, 0.15-0.64, respectively). Significantly fewer newborns had meconium below the vocal cords in the amnioinfusion group than in the control group (RR, 0.36; 95% CI, 0.13-0.97). Moreover, 14 newborns in the amnioinfusion group needed admission to the intensive care unit vs. 31 newborns in the control group. There were no significant differences between the 2 groups regarding the incidence rates of uterine hypertonus and maternal temperature higher than 38 degrees C. Therapeutic amnioinfusion is a simple and effective intervention that reduces the rates of cesarean section for intrapartum nonreassuring fetal heart tracing. In under-resourced settings, it can be performed using inexpensive catheters.

  17. Maternal obesity induces fibrosis in fetal myocardium of sheep

    PubMed Central

    Huang, Yan; Yan, Xu; Zhao, Jun X.; Zhu, Mei J.; McCormick, Richard J.; Ford, Stephen P.; Nathanielsz, Peter W.; Ren, Jun

    2010-01-01

    Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. The impact of MO on fetal myocardium development has received little attention. Fibrogenesis is regulated by the transforming growth factor-β (TGF-β)/p38 signaling pathway. Using the well-established model of MO in pregnant sheep, we evaluated the effect of MO on TGF-β/p38 and collagen accumulation in fetal myocardium. Nonpregnant ewes were assigned to a control diet [Con, fed 100% of National Research Council (NRC) nutrient recommendations] or obesogenic diet (OB, fed 150% of NRC recommendations) from 60 days before conception. Fetal ventricular muscle was sampled at 75 and 135 days of gestation (dG). At 75 dG, the expression of precursor TGF-β was 39.9 ± 9.9% higher (P < 0.05) in OB than Con fetal myocardium, consistent with the higher content of phosphorylated Smad3 in OB myocardium. The phosphorylation of p38 tended to be higher in OB myocardium (P = 0.08). In addition, enhanced Smad complexes were bound to Smad-binding elements in 75 dG OB fetal myocardium measured by DNA mobility shift assay (130.2 ± 26.0% higher, P < 0.05). Similar elevation of TGF-β signaling was observed in OB fetal myocardium at 135 dG. Total collagen concentration in OB was greater than Con fetal myocardium (2.42 ± 0.16 vs. 1.87 ± 0.04%, P < 0.05). Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 were higher in the Con group compared with OB sheep (43.86 ± 16.01 and 37.23 ± 7.97% respectively, P < 0.05). In summary, MO results in greater fetal heart connective tissue accumulation associated with an upregulated TGF-β/p38 signaling pathway at late gestation; such changes would be expected to negatively impact offspring heart function. PMID:20876759

  18. Update on Fetal Monitoring: Overview of Approaches and Management of Category II Tracings.

    PubMed

    Raghuraman, Nandini; Cahill, Alison G

    2017-12-01

    Electronic fetal monitoring (EFM) is widely used to assess fetal status in labor. Use of intrapartum continuous EFM is associated with a lower risk of neonatal seizures but a higher risk of cesarean or operative delivery. Category II fetal heart tracings (FHTs) are indeterminate in their ability to predict fetal acidemia. Certain patterns of decelerations and variability within this category may be predictive of neonatal morbidity. Adjunct tests of fetal well-being can be used during labor to further triage patients. Intrauterine resuscitation techniques should target the suspected etiology of intrapartum fetal hypoxia. Clinical factors play a role in the interpretation of EFM. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The Vascular Microarchitecture of the Human Fetal Pancreas: A Corrosion Casting and Scanning Electron Microscopy Study.

    PubMed

    Gorczyca, Janusz; Tomaszewski, Krzysztof A; Henry, Brandon Michael; Pękala, Przemysław Andrzej; Pasternak, Artur; Mizia, Ewa; Walocha, Jerzy A

    2017-01-01

    Detailed knowledge on the development of the pancreas is required to understand the variability in its blood supply. The aim of our study was to use the corrosion casting method combined with scanning electron microscopy to study the organization of the pancreatic microcirculation in human fetuses. The study was conducted on 28 human fetuses aged 18 to 25 gestational weeks. The fetal vasculature was appropriately prepared and then perfused with a low-viscosity Mercox CL-2R resin. The prepared vascular casts of the surface of the fetal pancreas were then examined in scanning electron microscopy and digitally analyzed. The lobular structure of the pancreas has a strong impact on the organization of the microvasculature. The lobular networks were supplied by the interlobular arteries and drained by the interlobular veins. The vascular system of fetal human pancreas has many portal connections, including islet-lobule and islet-duct portal circulations, which likely play a key role in the coordination of both endocrine and exocrine pancreatic functions. The organization of the microvascular network of the human pancreas in fetuses aged 18 to 25 gestational weeks is very similar to that of an adult but with more prominent features suggesting active processes of angiogenesis and vascular remodeling.

  20. Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells.

    PubMed

    Qiu, Caihong; Olivier, Emmanuel N; Velho, Michelle; Bouhassira, Eric E

    2008-02-15

    We have previously shown that coculture of human embryonic stem cells (hESCs) for 14 days with immortalized fetal hepatocytes yields CD34(+) cells that can be expanded in serum-free liquid culture into large numbers of megaloblastic nucleated erythroblasts resembling yolk sac-derived cells. We show here that these primitive erythroblasts undergo a switch in hemoglobin (Hb) composition during late terminal erythroid maturation with the basophilic erythroblasts expressing predominantly Hb Gower I (zeta(2)epsilon(2)) and the orthochromatic erythroblasts hemoglobin Gower II (alpha(2)epsilon(2)). This suggests that the switch from Hb Gower I to Hb Gower II, the first hemoglobin switch in humans is a maturation switch not a lineage switch. We also show that extending the coculture of the hESCs with immortalized fetal hepatocytes to 35 days yields CD34(+) cells that differentiate into more developmentally mature, fetal liver-like erythroblasts, that are smaller, express mostly fetal hemoglobin, and can enucleate. We conclude that hESC-derived erythropoiesis closely mimics early human development because the first 2 human hemoglobin switches are recapitulated, and because yolk sac-like and fetal liver-like cells are sequentially produced. Development of a method that yields erythroid cells with an adult phenotype remains necessary, because the most mature cells that can be produced with current systems express less than 2% adult beta-globin mRNA.

  1. Understanding fetal physiology and second line monitoring during labor.

    PubMed

    Garabedian, C; De Jonckheere, J; Butruille, L; Deruelle, P; Storme, L; Houfflin-Debarge, V

    2017-02-01

    Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition and is one of the most common obstetric procedures. Second line methods of fetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography and to better identify fetuses at risk of intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal blood scalp samples, the modification of the myocardial oxygenation by the fetal ECG ST-segment analysis (STAN) and the autonomic nervous system by the power spectral analysis of the fetal heart variability. To correctly interpret the features observed on CTG traces or second line methods, it seems important to understand normal physiology during labor and the compensatory mechanisms of the fetus in case of hypoxemia. Therefore, the aim of this review is first to describe fetal physiology during labor and then to explain the modification of the second line monitoring during labor. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. The Living Heart Project: A robust and integrative simulator for human heart function.

    PubMed

    Baillargeon, Brian; Rebelo, Nuno; Fox, David D; Taylor, Robert L; Kuhl, Ellen

    2014-11-01

    The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve.

  3. Phenotypic and in vivo functional characterization of immortalized human fetal liver cells.

    PubMed

    Patil, Pradeep B; Begum, Setara; Joshi, Meghnad; Kleman, Marika I; Olausson, Michael; Sumitran-Holgersson, Suchitra

    2014-06-01

    We report the establishment and characterization of immortalized human fetal liver progenitor cells by expression of the Simian virus 40 large T (SV40 LT) antigen. Well-characterized cells at various passages were transplanted into nude mice with acute liver injury and tested for functional capacity. The SV40LT antigen-immortalized fetal liver cells showed a morphology similar to primary cells. Cultured cells demonstrated stable phenotypic expression in various passages, of hepatic markers such as albumin, CK 8, CK18, transcription factors HNF-4α and HNF-1α and CYP3A/7. The cells did not stain for any of the tested cancer-associated markers. Albumin, HNF-4α and CYP3A7 expression was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Flow cytometry showed expression of some progenitor cell markers. In vivo study showed that the cells expressed both fetal and differentiated hepatocytes markers. Our study suggests new approaches to expand hepatic progenitor cells, analyze their fate in animal models aiming at cell therapy of hepatic diseases.

  4. Ontogeny of a novel pituitary protein (7B2) in the human fetal intestine.

    PubMed

    Suzuki, H; Christofides, N D; Adrian, T E; Chretien, M; Seidah, N G; Polak, J M; Bloom, S R

    1985-11-28

    The developmental profile of the concentration of a novel pituitary protein (7B2) was studied immunochemically in the human gastrointestinal tract from 12 weeks of gestation to 4 months after birth and was compared to the distribution in the adult. 7B2-like immunoreactivity (IR-7B2) was detected in all segments studied, but no gross changes were seen through fetal life. At term higher concentrations of IR-7B2 were found in the duodenum and the antrum, which is similar to the distribution of adult man. Gel permeation chromatography revealed that the main peak of 7B2 immunoreactivity in the fetal intestinal extract eluted with a Kav of 0.3. Similar elution profiles were also observed in extracts of human adult intestine.

  5. Production of embryonic and fetal-like red blood cells from human induced pluripotent stem cells.

    PubMed

    Chang, Chan-Jung; Mitra, Koyel; Koya, Mariko; Velho, Michelle; Desprat, Romain; Lenz, Jack; Bouhassira, Eric E

    2011-01-01

    We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications.

  6. Discovery of novel heart rate-associated loci using the Exome Chip

    PubMed Central

    van den Berg, Marten E.; Warren, Helen R.; Cabrera, Claudia P.; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A.; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J.; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A.; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V.; Lyytikäinen, Leo-Pekka; Hall, Leanne M.; van Setten, Jessica; Trompet, Stella; Prins, Bram P.; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A.; Silva, Claudia T.; Alonso, Alvaro; Bis, Joshua C.; de Boer, Rudolf; de Haan, Hugoline G.; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F.; Doney, Alex S. F.; Ellinor, Patrick T.; Eppinga, Ruben N.; Felix, Stephan B.; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B.; Heckbert, Susan R.; Huang, Paul L.; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K.; Kolcic, Ivana; Launer, Lenore J.; Li, Man; Yao, Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W.; Mangino, Massimo; Morris, Andrew D.; Mulas, Antonella; Murray, Alison D.; Nelson, Christopher P.; Orrú, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J.; Poulter, Neil; Psaty, Bruce M.; Qi, Lihong; Raitakari, Olli T.; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F.; Soliman, Elsayed Z.; Spector, Timothy D.; Stanton, Alice V.; Stirrups, Kathleen E.; Taylor, Kent D.; Tobin, Martin D.; Uitterlinden, André; Vaartjes, Ilonca; Hoes, Arno W.; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornelia M.; Zeggini, Eleftheria; Jukema, J. Wouter; Asselbergs, Folkert W.; Samani, Nilesh J.; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A.; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J.; Palmer, Colin N. A.; Sanna, Serena; Mook-Kanamori, Dennis O.; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I.; Dörr, Marcus; O'Donnell, Chris J.; Hayward, Caroline; Arking, Dan E.; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H.; Munroe, Patricia B.

    2017-01-01

    Abstract Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies. PMID:28379579

  7. Discovery of novel heart rate-associated loci using the Exome Chip.

    PubMed

    van den Berg, Marten E; Warren, Helen R; Cabrera, Claudia P; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V; Lyytikäinen, Leo-Pekka; Hall, Leanne M; van Setten, Jessica; Trompet, Stella; Prins, Bram P; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A; Silva, Claudia T; Alonso, Alvaro; Bis, Joshua C; de Boer, Rudolf; de Haan, Hugoline G; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F; Doney, Alex S F; Ellinor, Patrick T; Eppinga, Ruben N; Felix, Stephan B; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B; Heckbert, Susan R; Huang, Paul L; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K; Kolcic, Ivana; Launer, Lenore J; Li, Man; Yao, Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W; Mangino, Massimo; Morris, Andrew D; Mulas, Antonella; Murray, Alison D; Nelson, Christopher P; Orrú, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J; Poulter, Neil; Psaty, Bruce M; Qi, Lihong; Raitakari, Olli T; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F; Soliman, Elsayed Z; Spector, Timothy D; Stanton, Alice V; Stirrups, Kathleen E; Taylor, Kent D; Tobin, Martin D; Uitterlinden, André; Vaartjes, Ilonca; Hoes, Arno W; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornelia M; Zeggini, Eleftheria; Jukema, J Wouter; Asselbergs, Folkert W; Samani, Nilesh J; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J; Palmer, Colin N A; Sanna, Serena; Mook-Kanamori, Dennis O; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I; Dörr, Marcus; O'Donnell, Chris J; Hayward, Caroline; Arking, Dan E; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H; Munroe, Patricia B

    2017-06-15

    Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies. © The Author 2017. Published by Oxford University Press.

  8. A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep

    PubMed Central

    Herrera, E A; Kane, A D; Hansell, J A; Thakor, A S; Allison, B J; Niu, Y; Giussani, D A

    2012-01-01

    Virtually nothing is known about the effects on fetal physiology of xanthine oxidase inhibition. This is despite maternal treatment with the xanthine oxidase inhibitor allopurinol being considered in human complicated pregnancy to protect the infant's brain from excessive generation of ROS. We investigated the in vivo effects of maternal treatment with allopurinol on fetal cardiovascular function in ovine pregnancy in late gestation. Under anaesthesia, pregnant ewes and their singleton fetus were instrumented with vascular catheters and flow probes around an umbilical and a fetal femoral artery at 118 ± 1 dGA (days of gestational age; term ca. 145 days). Five days later, mothers were infused i.v. with either vehicle (n= 11) or allopurinol (n= 10). Fetal cardiovascular function was stimulated with increasing bolus doses of phenylephrine (PE) following maternal vehicle or allopurinol. The effects of maternal allopurinol on maternal and fetal cardiovascular function were also investigated following fetal NO blockade (n= 6) or fetal β1-adrenergic antagonism (n= 7). Maternal allopurinol led to significant increases in fetal heart rate, umbilical blood flow and umbilical vascular conductance, effects abolished by fetal β1-adrenergic antagonism but not by fetal NO blockade. Maternal allopurinol impaired fetal α1-adrenergic pressor and femoral vasopressor responses and enhanced the gain of the fetal cardiac baroreflex. These effects of maternal allopurinol were restored to control levels during fetal NO blockade. Maternal treatment with allopurinol induced maternal hypotension, tachycardia and acid–base disturbance. We conclude that maternal treatment with allopurinol alters in vivo maternal, umbilical and fetal vascular function via mechanisms involving NO and β1-adrenergic stimulation. The evidence suggests that the use of allopurinol in clinical practice should be approached with caution. PMID:22331413

  9. Fractal Analysis and Hurst Parameter for Intrapartum Fetal Heart Rate Variability Analysis: A Versatile Alternative to Frequency Bands and LF/HF Ratio

    PubMed Central

    Doret, Muriel; Spilka, Jiří; Chudáček, Václav; Gonçalves, Paulo; Abry, Patrice

    2015-01-01

    Background The fetal heart rate (FHR) is commonly monitored during labor to detect early fetal acidosis. FHR variability is traditionally investigated using Fourier transform, often with adult predefined frequency band powers and the corresponding LF/HF ratio. However, fetal conditions differ from adults and modify spectrum repartition along frequencies. Aims This study questions the arbitrariness definition and relevance of the frequency band splitting procedure, and thus of the calculation of the underlying LF/HF ratio, as efficient tools for characterizing intrapartum FHR variability. Study Design The last 30 minutes before delivery of the intrapartum FHR were analyzed. Subjects Case-control study. A total of 45 singletons divided into two groups based on umbilical cord arterial pH: the Index group with pH ≤ 7.05 (n = 15) and Control group with pH > 7.05 (n = 30). Outcome Measures Frequency band-based LF/HF ratio and Hurst parameter. Results This study shows that the intrapartum FHR is characterized by fractal temporal dynamics and promotes the Hurst parameter as a potential marker of fetal acidosis. This parameter preserves the intuition of a power frequency balance, while avoiding the frequency band splitting procedure and thus the arbitrary choice of a frequency separating bands. The study also shows that extending the frequency range covered by the adult-based bands to higher and lower frequencies permits the Hurst parameter to achieve better performance for identifying fetal acidosis. Conclusions The Hurst parameter provides a robust and versatile tool for quantifying FHR variability, yields better acidosis detection performance compared to the LF/HF ratio, and avoids arbitrariness in spectral band splitting and definitions. PMID:26322889

  10. Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

    PubMed

    Clancy, Robert M; Markham, Androo J; Jackson, Tanisha; Rasmussen, Sara E; Blumenberg, Miroslav; Buyon, Jill P

    2017-09-01

    The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S -adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes

  11. Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

    PubMed Central

    Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

    2010-01-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than < 3 %, whereas the transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to

  12. Prediction of fetal compromise in labor.

    PubMed

    Prior, Tomas; Mullins, Edward; Bennett, Phillip; Kumar, Sailesh

    2014-06-01

    The majority of intrapartum fetal hypoxia occurs in uncomplicated pregnancies. Current intrapartum monitoring techniques have not resulted in a reduction in the incidence of cerebral palsy in term neonates. We report the development of a composite risk score to allow risk stratification of normal pregnancies before labor. Six hundred one women were recruited to this prospective observational study. All women underwent an ultrasound examination before active labor, during which fetal biometry and fetal Doppler flow resistance indices were measured. A composite risk score, amalgamating data from the umbilical artery, middle cerebral artery, and umbilical vein, was then developed and correlated with intrapartum outcomes. In cases with the highest composite risk scores, the incidence of fetal compromise (the primary outcome) was 80.0% compared with just 15.3% in cases with the lowest risk scores (relative risk 5.2, 95% confidence interval 2.7-10.1). These cases were also at increased risk of cesarean delivery (53.3% compared with 3.4%, P<.001) and of developing a fetal heart rate pattern considered pathologic by National Institute for Health and Clinical Excellence criteria (P=.003). No significant variation in Apgar scores or umbilical artery pH was observed. Intrapartum fetal compromise remains a significant global health issue. The composite risk score reported here can identify fetuses at both high risk and low risk of a subsequent diagnosis of intrapartum fetal compromise. This may enable more judicious use of current intrapartum fetal monitoring techniques, which are hampered by low specificity. II.

  13. Fetal heart rate monitoring of short term variation (STV): a methodological observational study.

    PubMed

    Wretler, Stina; Holzmann, Malin; Graner, Sophie; Lindqvist, Pelle; Falck, Susanne; Nordström, Lennart

    2016-03-16

    Cardiotocography (CTG) has high sensitivity, but less specificity in detection of fetal hypoxia. There is need for adjunctive methods easy to apply during labor. Low fetal heart rate short term variation (STV) is predictive for hypoxia during the antenatal period. The objectives of our study were to methodologically evaluate monitoring of STV during labor and to compare two different monitors (Sonicaid™ and EDAN™) for antenatal use. A prospective observational study at the obstetric department, Karolinska University hospital, Stockholm (between September 2011 and April 2015). In 100 women of ≥ 36 weeks gestation, STV values were calculated during active labor. In a subset of 20 women we compared STV values between internal and external signal acquisition. Additionally we compared antenatal monitoring with two different monitors in another 20 women. Median STV in 100 fetuses monitored with scalp electrode during labor (EDAN™) was 7.1 msec (range 1.3-25.9) with no difference between early (3-6 cm) and late (7-10 cm) labor (7.1 vs 6.8 msec; p = 0.80). STV calculated from scalp electrode signals were positively correlated with delta-STV (STV internal -external) (R = 0.70; p < 0.01). No significant differences were found between Sonicaid™ and EDAN™ in antenatal external monitoring of STV (median difference 0.9 msec, Spearman Rank Correlation Sonicaid vs delta-STV; R = 0.35; p = 0.14). Median intrapartum STV was 7.1 msec. Significant differences were found between internal and external signal acquisition, a finding that suggests further intrapartum studies to be analysed separately depending upon type of signal acquisition. Antenatal external monitoring with Sonicaid™ and EDAN™ indicates that the devices perform equally well in the identification of acidemic fetuses. Further studies are needed to assess the clinical value of intrapartum STV.

  14. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

    PubMed

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

    2015-02-15

    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development. Copyright © 2015 the American Physiological

  15. Central vagal sensory and motor connections: human embryonic and fetal development.

    PubMed

    Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

    2004-07-30

    The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

  16. Maternal high-fat diet is associated with impaired fetal lung development

    PubMed Central

    Mayor, Reina S.; Finch, Katelyn E.; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D.; Frank, Aaron P.; Hahner, Lisa D.; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F.; Rosenfeld, Charles R.; Savani, Rashmin C.

    2015-01-01

    Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development. PMID:26092997

  17. Universal characteristics of evolution and development are inherent in fetal autonomic brain maturation.

    PubMed

    Schmidt, Alexander; Schukat-Talamazzini, Ernst G; Zöllkau, Janine; Pytlik, Adelina; Leibl, Sophia; Kumm, Kathrin; Bode, Franziska; Kynass, Isabelle; Witte, Otto W; Schleussner, Ekkehard; Schneider, Uwe; Hoyer, Dirk

    2018-07-01

    Adverse prenatal environmental influences to the developing fetus are associated with mental and cardiovascular disease in later life. Universal developmental characteristics such as self-organization, pattern formation, and adaptation in the growing information processing system have not yet been sufficiently analyzed with respect to description of normal fetal development and identification of developmental disturbances. Fetal heart rate patterns are the only non-invasive order parameter of the developing autonomic brain available with respect to the developing complex organ system. The objective of the present study was to investigate whether universal indices, known from evolution and phylogeny, describe the ontogenetic fetal development from 20 weeks of gestation onwards. By means of a 10-fold cross-validated data-driven multivariate regression modeling procedure, relevant indices of heart rate variability (HRV) were explored using 552 fetal heart rate recordings, each lasting over 30 min. We found that models which included HRV indices of increasing fluctuation amplitude, complexity and fractal long-range dependencies largely estimated the maturation age (coefficients of determination 0.61-0.66). Consideration of these characteristics in prenatal care may not only have implications for early identification of developmental disturbances, but also for the development of system-theory-based therapeutic strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers

    PubMed Central

    Moscovitz, Jamie E.; Nahar, Muna S.; Shalat, Stuart L.; Slitt, Angela L.; Dolinoy, Dana C.

    2016-01-01

    Because of its widespread use in the manufacturing of consumer products over several decades, human exposure to bisphenol A (BPA) has been pervasive. Fetuses are particularly sensitive to BPA exposure, with a number of negative developmental and reproductive outcomes observed in rodent perinatal models. Xenobiotic transporters are one mechanism to extrude conjugated and unconjugated BPA from the liver. In this study, the mRNA expression of xenobiotic transporters and relationships with total, conjugated, and free BPA levels were explored utilizing human fetal liver samples. The mRNA expression of breast cancer resistance protein (BCRP) and multidrug resistance-associated transporter (MRP)4, as well as BCRP and multidrug resistance transporter 1 exhibited the highest degree of correlation, with r2 values of 0.941 and 0.816 (P < 0.001 for both), respectively. Increasing concentrations of conjugated BPA significantly correlated with high expression of MRP1 (P < 0.001), MRP2 (P < 0.05), and MRP3 (P < 0.05) transporters, in addition to the NF-E2–related factor 2 transcription factor (P < 0.001) and its prototypical target gene, NAD(P)H quinone oxidoreductase 1 (P < 0.001). These data demonstrate that xenobiotic transporters may be coordinately expressed in the human fetal liver. This is also the first report of a relationship between environmentally relevant fetal BPA levels and differences in the expression of transporters that can excrete the parent compound and its metabolites. PMID:26851240

  19. Increased Cardiac Myocyte Progenitors in Failing Human Hearts

    PubMed Central

    Kubo, Hajime; Jaleel, Naser; Kumarapeli, Asangi; Berretta, Remus M.; Bratinov, George; Shan, Xiaoyin; Wang, Hongmei; Houser, Steven R.; Margulies, Kenneth B.

    2009-01-01

    Background Increasing evidence, derived mainly from animal models, supports the existence of endogenous cardiac renewal and repair mechanisms in adult mammalian hearts that could contribute to normal homeostasis and the responses to pathological insults. Methods and Results Translating these results, we isolated small c-kit+ cells from 36 of 37 human hearts using primary cell isolation techniques and magnetic cell sorting techniques. The abundance of these cardiac progenitor cells was increased nearly 4-fold in patients with heart failure requiring transplantation compared with nonfailing controls. Polychromatic flow cytometry of primary cell isolates (<30 μm) without antecedent c-kit enrichment confirmed the increased abundance of c-kit+ cells in failing hearts and demonstrated frequent coexpression of CD45 in these cells. Immunocytochemical characterization of freshly isolated, c-kit–enriched human cardiac progenitor cells confirmed frequent coexpression of c-kit and CD45. Primary cardiac progenitor cells formed new human cardiac myocytes at a relatively high frequency after coculture with neonatal rat ventricular myocytes. These contracting new cardiac myocytes exhibited an immature phenotype and frequent electric coupling with the rat myocytes that induced their myogenic differentiation. Conclusions Despite the increased abundance and cardiac myogenic capacity of cardiac progenitor cells in failing human hearts, the need to replace these organs via transplantation implies that adverse features of the local myocardial environment overwhelm endogenous cardiac repair capacity. Developing strategies to improve the success of endogenous cardiac regenerative processes may permit therapeutic myocardial repair without cell delivery per se. PMID:18645055

  20. Phase Transition in a Healthy Human Heart Rate

    NASA Astrophysics Data System (ADS)

    Kiyono, Ken; Struzik, Zbigniew R.; Aoyagi, Naoko; Togo, Fumiharu; Yamamoto, Yoshiharu

    2005-07-01

    A healthy human heart rate displays complex fluctuations which share characteristics of physical systems in a critical state. We demonstrate that the human heart rate in healthy individuals undergoes a dramatic breakdown of criticality characteristics, reminiscent of continuous second order phase transitions. By studying the germane determinants, we show that the hallmark of criticality—highly correlated fluctuations—is observed only during usual daily activity, and a breakdown of these characteristics occurs in prolonged, strenuous exercise and sleep. This finding is the first reported discovery of the dynamical phase transition phenomenon in a biological control system and will be a key to understanding the heart rate control system in health and disease.

  1. Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Newby, Elizabeth A.; Myers, Dean A.

    2015-01-01

    In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus. PMID:26173460

  2. Validation of In utero Tractography of Human Fetal Commissural and Internal Capsule Fibers with Histological Structure Tensor Analysis

    PubMed Central

    Mitter, Christian; Jakab, András; Brugger, Peter C.; Ricken, Gerda; Gruber, Gerlinde M.; Bettelheim, Dieter; Scharrer, Anke; Langs, Georg; Hainfellner, Johannes A.; Prayer, Daniela; Kasprian, Gregor

    2015-01-01

    Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic

  3. A Device for Fetal Monitoring by Means of Control Over Cardiovascular Parameters Based on Acoustic Data

    NASA Astrophysics Data System (ADS)

    Khokhlova, L. A.; Seleznev, A. I.; Zhdanov, D. S.; Zemlyakov, I. Yu; Kiseleva, E. Yu

    2016-01-01

    The problem of monitoring fetal health is topical at the moment taking into account a reduction in the level of fertile-age women's health and changes in the concept of perinatal medicine with reconsideration of live birth criteria. Fetal heart rate monitoring is a valuable means of assessing fetal health during pregnancy. The routine clinical measurements are usually carried out by the means of ultrasound cardiotocography. Although the cardiotocography monitoring provides valuable information on the fetal health status, the high quality ultrasound devices are expensive, they are not available for home care use. The recommended number of measurement is also limited. The passive and fully non-invasive acoustic recording provides an alternative low-cost measurement method. The article describes a device for fetal and maternal health monitoring by analyzing the frequency and periodicity of heart beats by means of acoustic signal received on the maternal abdomen. Based on the usage of this device a phonocardiographic fetal telemedicine system, which will allow to reduce the antenatal fetal mortality rate significantly due to continuous monitoring over the state of fetus regardless of mother's location, can be built.

  4. Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts.

    PubMed

    Garreta, Elena; de Oñate, Lorena; Fernández-Santos, M Eugenia; Oria, Roger; Tarantino, Carolina; Climent, Andreu M; Marco, Andrés; Samitier, Mireia; Martínez, Elena; Valls-Margarit, Maria; Matesanz, Rafael; Taylor, Doris A; Fernández-Avilés, Francisco; Izpisua Belmonte, Juan Carlos; Montserrat, Nuria

    2016-08-01

    Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Pregnancy outcome of threatened abortion with demonstrable fetal cardiac activity: a cohort study.

    PubMed

    Tongsong, T; Srisomboon, J; Wanapirak, C; Sirichotiyakul, S; Pongsatha, S; Polsrisuthikul, T

    1995-08-01

    Pregnancy with visible fetal heart beat complicated by first trimester threatened abortion had significant increased risk of subsequent spontaneous abortion compared with normal pregnancy. To compare pregnancy outcomes in cases complicated by first trimester threatened abortion with those that were not. Prospective cohort study of 255 cases of first trimester threatened abortions but with visible heart beat and 265 other normal pregnancies. Spontaneous abortion rates of 5.5% (with relative abortal risk of 2.91) was found for study group, compared to 1.88% for controls (p < 0.05). Preterm delivery was also higher, but was not statistically significant. First trimester bleeding with visible fetal heart beat appears to associate significantly with higher subsequent spontaneous abortion rate than those without.

  6. Influence of maternal body mass index on accuracy and reliability of external fetal monitoring techniques.

    PubMed

    Cohen, Wayne R; Hayes-Gill, Barrie

    2014-06-01

    To evaluate the performance of external electronic fetal heart rate and uterine contraction monitoring according to maternal body mass index. Secondary analysis of prospective equivalence study. Three US urban teaching hospitals. Seventy-four parturients with a normal term pregnancy. The parent study assessed performance of two methods of external fetal heart rate monitoring (abdominal fetal electrocardiogram and Doppler ultrasound) and of uterine contraction monitoring (electrohystero-graphy and tocodynamometry) compared with internal monitoring with fetal scalp electrode and intrauterine pressure transducer. Reliability of external techniques was assessed by the success rate and positive percent agreement with internal methods. Bland-Altman analysis determined accuracy. We analyzed data from that study according to maternal body mass index. We assessed the relationship between body mass index and monitor performance with linear regression, using body mass index as the independent variable and measures of reliability and accuracy as dependent variables. There was no significant association between maternal body mass index and any measure of reliability or accuracy for abdominal fetal electrocardiogram. By contrast, the overall positive percent agreement for Doppler ultrasound declined (p = 0.042), and the root mean square error from the Bland-Altman analysis increased in the first stage (p = 0.029) with increasing body mass index. Uterine contraction recordings from electrohysterography and tocodynamometry showed no significant deterioration related to maternal body mass index. Accuracy and reliability of fetal heart rate monitoring using abdominal fetal electrocardiogram was unaffected by maternal obesity, whereas performance of ultrasound degraded directly with maternal size. Both electrohysterography and tocodynamometry were unperturbed by obesity. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  7. Utility of fetal cardiac magnetic resonance imaging to assess fetuses with right aortic arch and right ductus arteriosus.

    PubMed

    Dong, Su-Zhen; Zhu, Ming

    2018-06-01

    To evaluate the utility of fetal cardiac magnetic resonance imaging (MRI) to diagnose right aortic arch (RAA) with right ductus arteriosus. This retrospective study included six fetuses with right aortic arch and right ductus arteriosus. The six fetal cases were examined using a 1.5-T magnetic resonance unit. The steady-state free precession (SSFP) and single-shot turbo spin echo (SSTSE) sequences were used to evaluate the fetal heart and airway. The gestational age of the six fetuses ranged from 22 to 35 weeks (mean, 26.5 weeks). The age of the pregnant women ranged from 23 to 40 years (mean 31 years). Fetal cardiac MRI diagnosed the six fetal cases with RAA with right ductus arteriosus correctly. Among the six fetuses, four were associated with other congenital heart defects. In three of six cases, the diagnoses established using prenatal echocardiography (echo) was correct when compared with postnatal diagnosis. Fetal cardiac MRI is a useful complementary tool to assess fetuses with RAA and right ductus arteriosus.

  8. Time-lapse imaging of human heart motion with switched array UWB radar.

    PubMed

    Brovoll, Sverre; Berger, Tor; Paichard, Yoann; Aardal, Øyvind; Lande, Tor Sverre; Hamran, Svein-Erik

    2014-10-01

    Radar systems for detection of human heartbeats have mostly been single-channel systems with limited spatial resolution. In this paper, a radar system for ultra-wideband (UWB) imaging of the human heart is presented. To make the radar waves penetrate the human tissue the antenna is placed very close to the body. The antenna is an array with eight elements, and an antenna switch system connects the radar to the individual elements in sequence to form an image. Successive images are used to build up time-lapse movies of the beating heart. Measurements on a human test subject are presented and the heart motion is estimated at different locations inside the body. The movies show rhythmic motion consistent with the beating heart, and the location and shape of the reflections correspond well with the expected response form the heart wall. The spatial dependent heart motion is compared to ECG recordings, and it is confirmed that heartbeat modulations are seen in the radar data. This work shows that radar imaging of the human heart may provide valuable information on the mechanical movement of the heart.

  9. Feasibility and reproducibility of a standard protocol for 2D speckle tracking and tissue Doppler-based strain and strain rate analysis of the fetal heart.

    PubMed

    Crispi, Fàtima; Sepulveda-Swatson, Eduardo; Cruz-Lemini, Monica; Rojas-Benavente, Juan; Garcia-Posada, Raul; Dominguez, Jesus Maria; Sitges, Marta; Bijnens, Bart; Gratacós, Eduard

    2012-01-01

    Assessment of cardiac function in the fetal heart is challenging because of its small size and high heart rate, restricted physical access to the fetus, and impossibility of fetal ECG recording. We aimed to standardize the acquisition and postprocessing of fetal echocardiography for deformation analysis and to assess its feasibility, reproducibility, and correlation for longitudinal strain and strain rate measurements by tissue Doppler imaging (TDI) and 2D speckle tracking (2D-strain) during pregnancy. Echocardiography was performed in 56 fetuses. 2D and color TDI in apical or basal four-chamber views were recorded for subsequent analysis. Caution was taken to achieve a frame rate >70 Hz for speckle tracking and >150 Hz for TDI analysis. For each acquisition, 7.5 s of noncompressed data were stored in cine loop format and analyzed offline. Since fetal ECG information is by definition not available, aortic valve closure was marked from aortic flow and the onset of each cardiac cycle was manually indicated in the 2D images. Sample volume length was standardized at the minimum size. Two observers measured the left and right ventricular peak systolic longitudinal strain and strain-rate. Strain and strain rate measurements were feasible in 93% of the TDI and 2D-strain acquisitions. The mean time spent on analyzing TDI images was 18 min, with an intraclass agreement coefficient of 0.86 (95% CI 0.77-0.92), 0.83 (95% CI 0.72-0.90), 0.96 (95% CI 0.93-0.98), and 0.86 (95% CI 0.76-0.92) for basal left and right free wall peak systolic strain and strain rate, respectively. Agreement between observers using tissue Doppler also showed high reliability. The mean time spent for 2D-strain analysis was 15 min, with an intraclass agreement coefficient of 0.97 (95% CI 0.95-0.98), 0.94 (95% CI 0.89-0.96), 0.96 (95% CI 0.93-0.98), and 0.84 (95% CI 0.73-0.90) for basal left and right free wall peak systolic strain and strain rate, respectively. Agreement between observers also showed a

  10. CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

    PubMed

    Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

    1992-12-01

    The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

  11. Nonlinear analysis of fetal heart rate dynamics in fetuses compromised by asymptomatic partial placental abruption.

    PubMed

    Choi, Won-Young; Hoh, Jeong-Kyu

    2015-12-01

    We analyzed fetal heart rate (FHR) parameters, dynamics, and outcomes in pregnancies with asymptomatic partial placental abruption (PPA) compared with those in normal pregnancies. We examined nonstress test (NST) data acquired from 2003 to 2012 at our institution. Normal pregnancies (N = 170) and PPA cases (N = 17) were matched for gestational age, fetal sex, and mean FHR. NSTs were performed at 33-42 weeks of gestation. FHR parameters obtained from the NST and perinatal outcomes were analyzed using linear methods. Nonlinear indices, including approximate entropy (ApEn), sample entropy (SampEn), short-term and long-term scaling exponents (α1 and α2), and correlation dimension (CD), were used to interpret FHR dynamics and system complexity. The area under a receiver operating characteristic curve (AUC) was used to evaluate the nonlinear indices. There were no significant differences in general characteristics and FHR parameters between the PPA and control groups. However, gestational age at delivery, birth weight, 5-min Apgar scores, ApEn, SampEn, and CD were significantly lower in the PPA group than in the control group (P < 0.05). The long-term scaling exponent (α2) and crossover index (α2/α1) of the PPA fetuses were significantly higher than those of the controls (P < 0.01). A multiple regression model showed better performance in predicting PPA (AUC, 0.92; sensitivity 82.35%; specificity, 94.12%). Nonlinear dynamic indices of FHR in asymptomatic PPA were qualitatively different from those in normal pregnancies, whereas the conventional FHR parameters were not significantly different. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

    PubMed

    Dos Remedios, C G; Lal, S P; Li, A; McNamara, J; Keogh, A; Macdonald, P S; Cooke, R; Ehler, E; Knöll, R; Marston, S B; Stelzer, J; Granzier, H; Bezzina, C; van Dijk, S; De Man, F; Stienen, G J M; Odeberg, J; Pontén, F; Linke, W; van der Velden, J

    2017-08-01

    The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are

  13. Fetal Cardiac Responding: Maturational and Behavioral Correlates.

    ERIC Educational Resources Information Center

    Emory, Eugene K.; Noonan, John R.

    1984-01-01

    Classified fetuses as accelerators or decelerators based on intrapartum fetal heart rate (FHR). Explored the relationship of the classification with gestational age and neonatal behavior in clinically healthy neonates to provide an empirical basis for using FHR in the study of infant behavior. Subjects were 48 "healthy term" or…

  14. A Percutaneously Implantable Fetal Pacemaker

    PubMed Central

    Zhou, Li; Vest, Adriana N.; Chmait, Ramen H.; Bar-Cohen, Yaniv; Pruetz, Jay; Silka, Michael; Zheng, Kaihui; Peck, Ray; Loeb, Gerald E.

    2015-01-01

    A miniaturized, self-contained pacemaker that could be implanted with a minimally invasive technique would dramatically improve the survival rate for fetuses that develop hydrops fetalis as a result of congenital heart block. We are currently validating a device that we developed to address this bradyarrhythmia. Preclinical studies in a fetal sheep model are underway to demonstrate that the device can be implanted via a minimally invasive approach, can mechanically withstand the harsh bodily environment, can induce effective contractions of the heart muscle with an adequate safety factor, and can successfully operate for the required device lifetime of three months using the previously-developed closed loop transcutaneous recharging system. PMID:25570982

  15. Telemedicine to Improve Access to Specialist Care in Fetal Heart Rate Monitoring: Analysis of 17 Years of TOCOMAT Network Clinical Activity.

    PubMed

    Tagliaferri, Salvatore; Esposito, Francesca Giovanna; Ippolito, Adelaide; Mereghini, Flavia; Magenes, Giovanni; Martinelli, Pasquale; Campanile, Marta; Signorini, Maria Gabriella

    2017-03-01

    The objective of this article is to provide an overview of the clinical experience of our telemedicine network (TOCOMAT) for fetal well-being assessment through computerized Cardiotocography (cCTG), analyzing cultural, socioeconomic, and environmental conditions of pregnant women and its economic sustainability over time. We used the central data store, including all cCTG records collected in Campania region (Italy) during 17 years of activity. The Operations Center acquires the traces recorded in the Remote Units and simultaneously performs a complex fetal heart rate analysis. An Internet or phone conference calling is available to discuss the information transmitted. Finally, the report is send back to the Remote Units. The number of cCTG traces performed was constantly increasing, despite the progressive reduction in the number of peripheral units involved. Pregnant women in Remote Unit group were younger and overweight and showed a higher incidence of diabetes and fetal defects than Operations Center ones. Moreover, a high rate of African migrant women and low socioeconomic and cultural standards were found in Remote Unit group. The cost analysis showed an economic advantage both in the reduction of inappropriate admissions and in the improvement of admission indicators (hospital stay days) for pregnant women. The global economic recession has had a significant impact on the Italian regional healthcare system and socioeconomic deprivation. Telemedicine could avoid unnecessary referral to Level III centers (Hospital) in Campania region, where the average population density is very high, allowing equal access to ultra-specialist assessment irrespective of the geographical location of the pregnant woman with medium to high risk, as well as rationalizing the costs for maternal and fetal care.

  16. Developmental Change in Fetal Response to Repeated Low-Intensity Sound

    ERIC Educational Resources Information Center

    Morokuma, Seiichi; Doria, Valentina; Ierullo, Antonio; Kinukawa, Naoko; Fukushima, Kotaro; Nakano, Hitoo; Arulkumaran, Sabaratnam; Papageorghiou, Aris T.

    2008-01-01

    The aim of this study was to investigate developmental changes in heart rate response to repeated low-intensity (85 dB) sound stimulation in fetuses between 32 and 37 weeks of gestation. We measured amplitude changes in heart rate as our index of fetal response. At 35 to 37 weeks of gestation, the majority of fetuses showed a deceleratory response…

  17. Ultrasound investigation of fetal human upper respiratory anatomy.

    PubMed

    Wolfson, V P; Laitman, J T

    1990-07-01

    Although the human upper respiratory-upper digestive tract is an area of vital importance, relatively little is known about either the structural or functional changes that occur in the region during the fetal period. While investigations in our laboratory have begun to chart these changes through the use of postmortem materials, in vivo studies have been rarely attempted. This study combines ultrasonography with new applications of video editing to examine aspects of prenatal upper respiratory development. Structures of the fetal upper respiratory-digestive tract and their movements were studied through the use of ultrasonography and detailed frame-by-frame analysis. Twenty-five living fetuses, aged 18-36 weeks gestation, were studied in utero during routine diagnostic ultrasound examination. These real-time linear array sonograms were videotaped during each study. Videotapes were next analyzed for anatomical structures and movement patterns, played back through the ultrasound machine in normal speed, and then examined with a frame-by-frame video editor (FFVE) to identify structures and movements. Still images were photographed directly from the video monitor using a 35 mm camera. Results show that upper respiratory and digestive structures, as well as their movements, could be seen clearly during normal speed and repeat frame-by-frame analysis. Major structures that could be identified in the majority of subjects included trachea in 20 of 25 fetuses (80%); larynx, 76%; pharynx, 76%. Smaller structures were more variable, but were nevertheless observed on both sagittal and coronal section: piriform sinuses, 76%; thyroid cartilage, 36%; cricoid cartilage, 32%; and epiglottis, 16%. Movements of structures could also be seen and were those typically observed in connection with swallowing: fluttering tongue movements, changes in pharyngeal shape, and passage of a bolus via the piriform sinuses to esophagus. Fetal swallows had minimal laryngeal motion. This study

  18. Oxygen consumption of human heart cells in monolayer culture.

    PubMed

    Sekine, Kaori; Kagawa, Yuki; Maeyama, Erina; Ota, Hiroki; Haraguchi, Yuji; Matsuura, Katsuhisa; Shimizu, Tatsuya

    2014-09-26

    Tissue engineering in cardiovascular regenerative therapy requires the development of an efficient oxygen supply system for cell cultures. However, there are few studies which have examined human cardiomyocytes in terms of oxygen consumption and metabolism in culture. We developed an oxygen measurement system equipped with an oxygen microelectrode sensor and estimated the oxygen consumption rates (OCRs) by using the oxygen concentration profiles in culture medium. The heart is largely made up of cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells. Therefore, we measured the oxygen consumption of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), cardiac fibroblasts, human cardiac microvascular endothelial cell and aortic smooth muscle cells. Then we made correlations with their metabolisms. In hiPSC-CMs, the value of the OCR was 0.71±0.38pmol/h/cell, whereas the glucose consumption rate and lactate production rate were 0.77±0.32pmol/h/cell and 1.61±0.70pmol/h/cell, respectively. These values differed significantly from those of the other cells in human heart. The metabolism of the cells that constitute human heart showed the molar ratio of lactate production to glucose consumption (L/G ratio) that ranged between 1.97 and 2.2. Although the energy metabolism in adult heart in vivo is reported to be aerobic, our data demonstrated a dominance of anaerobic glycolysis in an in vitro environment. With our measuring system, we clearly showed the differences in the metabolism of cells between in vivo and in vitro monolayer culture. Our results regarding cell OCRs and metabolism may be useful for future tissue engineering of human heart. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Hypoxia: From Placental Development to Fetal Programming.

    PubMed

    Fajersztajn, Lais; Veras, Mariana Matera

    2017-10-16

    Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O 2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Inadequate fetal heart rate monitoring and poor use of partogram associated with intrapartum stillbirth: a case-referent study in Nepal.

    PubMed

    Kc, Ashish; Wrammert, Johan; Clark, Robert B; Ewald, Uwe; Målqvist, Mats

    2016-08-19

    Newborns are at the greatest risk for dying during the intrapartum period, including labor and delivery, and the first day of life. Fetal heart rate monitoring (FHRM) and partogram use to track labor progress are evidence-based techniques that can help to identify maternal and fetal risk factors so that these can be addressed early. The objective of this study was to assess health worker adherence to protocols for FHRM and partogram use during the intrapartum period, and to assess the association between adherence and intrapartum stillbirth in a tertiary hospital of Nepal. A case-referent study was conducted over a 15-month period. Cases included all intrapartum stillbirths, while 20 % of women with live births were randomly selected on admission to make up the referent population. The frequency of FHRM and the use of partogram were measured and their association to intrapartum stillbirth was assessed using logistic regression analysis. During the study period, 4,476 women with live births were enrolled as referents and 136 with intrapartum stillbirths as cases. FHRM every 30 min was only completed in one-fourth of the deliveries, and labor progress was monitored using a partogram in just over half. With decreasing frequency of FHRM, there was an increased risk of intrapartum stillbirth; FHRM at intervals of more than 30 min resulted in a four-fold risk increase for intrapartum stillbirth (aOR 4.17, 95 % CI 2.0-8.7), and the likelihood of intrapartum stillbirth increased seven times if FHRM was performed less than every hour or not at all (aOR 7.38, 95 % CI 3.5-15.4). Additionally, there was a three-fold increased risk of intrapartum stillbirth if the partogram was not used (aOR 3.31, 95 % CI 2.0-5.4). The adherence to FHRM and partogram use was inadequate for monitoring intrapartum progress in a tertiary hospital of Nepal. There was an increased risk of intrapartum stillbirth when fetal heart rate was inadequately monitored and when the progress of labor was

  1. [Fetal bradycardia: a retrospective study in 9 Spanish centers].

    PubMed

    Perin, F; Rodríguez Vázquez del Rey, M M; Deiros Bronte, L; Ferrer Menduiña, Q; Rueda Nuñez, F; Zabala Arguelles, J I; García de la Calzada, D; Teodoro Marin, S; Centeno Malfaz, F; Galindo Izquierdo, A

    2014-11-01

    The aim of this study is to review the current management and outcomes of fetal bradycardia in 9 Spanish centers. Retrospective multicenter study: analysis of all fetuses with bradycardia diagnosed between January 2008 and September 2010. Underlying mechanisms of fetal bradyarrhythmias were studied with echocardiography. A total of 37 cases were registered: 3 sinus bradycardia, 15 blocked atrial bigeminy, and 19 high grade atrioventricular blocks. Sinus bradycardia: 3 cases (100%) were associated with serious diseases. Blocked atrial bigeminy had an excellent outcome, except for one case with post-natal tachyarrhythmia. Of the atrioventricular blocks, 16% were related to congenital heart defects with isomerism, 63% related to the presence of maternal SSA/Ro antibodies, and 21% had unclear etiology. Overall mortality was 20% (37%, if terminations of pregnancy are taken into account). Risk factors for mortality were congenital heart disease, hydrops and/or ventricular dysfunction. Management strategies differed among centers. Steroids were administrated in 73% of immune-mediated atrioventricular blocks, including the only immune-mediated IInd grade block. More than half (58%) of atrioventricular blocks had a pacemaker implanted in a follow-up of 18 months. Sustained fetal bradycardia requires a comprehensive study in all cases, including those with sinus bradycardia. Blocked atrial bigeminy has a good prognosis, but tachyarrhythmias may develop. Heart block has significant mortality and morbidity rates, and its management is still highly controversial. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. Atrial fibrillation driver mechanisms: Insight from the isolated human heart.

    PubMed

    Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V

    2017-01-01

    Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Autonomic regulation in fetuses with Congenital Heart Disease

    PubMed Central

    Siddiqui, Saira; Wilpers, Abigail; Myers, Michael; Nugent, J. David; Fifer, William P.; Williams, Ismée A.

    2015-01-01

    Background Exposure to antenatal stressors affects autonomic regulation in fetuses. Whether the presence of congenital heart disease (CHD) alters the developmental trajectory of autonomic regulation is not known. Aims/Study Design This prospective observational cohort study aimed to further characterize autonomic regulation in fetuses with CHD; specifically hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF). Subjects From 11/2010 – 11/2012, 92 fetuses were enrolled: 41 controls and 51 with CHD consisting of 19 with HLHS, 12 with TGA, and 20 with TOF. Maternal abdominal fetal electrocardiogram (ECG) recordings were obtained at 3 gestational ages: 19-27 weeks (F1), 28-33 weeks (F2), and 34-38 weeks (F3). Outcome measures Fetal ECG was analyzed for mean heart rate along with 3 measures of autonomic variability of the fetal heart rate: interquartile range, standard deviation, and root mean square of the standard deviation of the heart rate (RMSSD), a measure of parasympathetic activity. Results During F1 and F2 periods, HLHS fetuses demonstrated significantly lower mean HR than controls (p<0.05). Heart rate variability at F3, as measured by standard deviation, interquartile range, and RMSSD was lower in HLHS than controls (p<0.05). Other CHD subgroups showed a similar, though non-significant trend towards lower variability. Conclusions Autonomic regulation in CHD fetuses differs from controls with HLHS fetuses most markedly affected. PMID:25662702

  4. Autonomic regulation in fetuses with congenital heart disease.

    PubMed

    Siddiqui, Saira; Wilpers, Abigail; Myers, Michael; Nugent, J David; Fifer, William P; Williams, Ismée A

    2015-03-01

    Exposure to antenatal stressors affects autonomic regulation in fetuses. Whether the presence of congenital heart disease (CHD) alters the developmental trajectory of autonomic regulation is not known. This prospective observational cohort study aimed to further characterize autonomic regulation in fetuses with CHD; specifically hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF). From 11/2010 to 11/2012, 92 fetuses were enrolled: 41 controls and 51 with CHD consisting of 19 with HLHS, 12 with TGA, and 20 with TOF. Maternal abdominal fetal electrocardiogram (ECG) recordings were obtained at 3 gestational ages: 19-27 weeks (F1), 28-33 weeks (F2), and 34-38 weeks (F3). Fetal ECG was analyzed for mean heart rate along with 3 measures of autonomic variability of the fetal heart rate: interquartile range, standard deviation, and root mean square of the standard deviation of the heart rate (RMSSD), a measure of parasympathetic activity. During F1 and F2 periods, HLHS fetuses demonstrated significantly lower mean HR than controls (p<0.05). Heart rate variability at F3, as measured by standard deviation, interquartile range, and RMSSD was lower in HLHS than controls (p<0.05). Other CHD subgroups showed a similar, though non-significant trend towards lower variability. Autonomic regulation in CHD fetuses differs from controls, with HLHS fetuses most markedly affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Ellipsoidal head model for fetal magnetoencephalography: forward and inverse solutions

    NASA Astrophysics Data System (ADS)

    Gutiérrez, David; Nehorai, Arye; Preissl, Hubert

    2005-05-01

    Fetal magnetoencephalography (fMEG) is a non-invasive technique where measurements of the magnetic field outside the maternal abdomen are used to infer the source location and signals of the fetus' neural activity. There are a number of aspects related to fMEG modelling that must be addressed, such as the conductor volume, fetal position and orientation, gestation period, etc. We propose a solution to the forward problem of fMEG based on an ellipsoidal head geometry. This model has the advantage of highlighting special characteristics of the field that are inherent to the anisotropy of the human head, such as the spread and orientation of the field in relationship with the localization and position of the fetal head. Our forward solution is presented in the form of a kernel matrix that facilitates the solution of the inverse problem through decoupling of the dipole localization parameters from the source signals. Then, we use this model and the maximum likelihood technique to solve the inverse problem assuming the availability of measurements from multiple trials. The applicability and performance of our methods are illustrated through numerical examples based on a real 151-channel SQUID fMEG measurement system (SARA). SARA is an MEG system especially designed for fetal assessment and is currently used for heart and brain studies. Finally, since our model requires knowledge of the best-fitting ellipsoid's centre location and semiaxes lengths, we propose a method for estimating these parameters through a least-squares fit on anatomical information obtained from three-dimensional ultrasound images.

  6. Integration of multivariate empirical mode decomposition and independent component analysis for fetal ECG separation from abdominal signals.

    PubMed

    Thanaraj, Palani; Roshini, Mable; Balasubramanian, Parvathavarthini

    2016-11-14

    The fetal electrocardiogram (FECG) signals are essential to monitor the health condition of the baby. Fetal heart rate (FHR) is commonly used for diagnosing certain abnormalities in the formation of the heart. Usually, non-invasive abdominal electrocardiogram (AbECG) signals are obtained by placing surface electrodes in the abdomen region of the pregnant woman. AbECG signals are often not suitable for the direct analysis of fetal heart activity. Moreover, the strength and magnitude of the FECG signals are low compared to the maternal electrocardiogram (MECG) signals. The MECG signals are often superimposed with the FECG signals that make the monitoring of FECG signals a difficult task. Primary goal of the paper is to separate the fetal electrocardiogram (FECG) signals from the unwanted maternal electrocardiogram (MECG) signals. A multivariate signal processing procedure is proposed here that combines the Multivariate Empirical Mode Decomposition (MEMD) and Independent Component Analysis (ICA). The proposed method is evaluated with clinical abdominal signals taken from three pregnant women (N= 3) recorded during the 38-41 weeks of the gestation period. The number of fetal R-wave detected (NEFQRS), the number of unwanted maternal peaks (NMQRS), the number of undetected fetal R-wave (NUFQRS) and the FHR detection accuracy quantifies the performance of our method. Clinical investigation with three test subjects shows an overall detection accuracy of 92.8%. Comparative analysis with benchmark signal processing method such as ICA suggests the noteworthy performance of our method.

  7. High-resolution imaging diagnosis of human fetal membrane by three-dimensional optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ren, Hugang; Avila, Cecilia; Kaplan, Cynthia; Pan, Yingtian

    2011-11-01

    Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane (FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of high-scattering decidua vera (DV, average thickness dDV ~ 92+/-38 μm), low-scattering chorion and trophoblast (CT, dCT ~ 150+/-67 μm), high-scattering subepithelial amnion (A, dA ~ 95+/-36 μm), and low-scattering epithelium (E, dE ~ 29+/-8 μm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to edema, fluid buildup, vasodilatation) and track (staging) their thicknesses dMCP ranging from 24 to 615 μm. It was also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker MCPs (e.g., dMCP>615 μm) because of its increased imaging depth.

  8. Unshielded fetal magnetocardiography system using two-dimensional gradiometers

    NASA Astrophysics Data System (ADS)

    Seki, Yusuke; Kandori, Akihiko; Kumagai, Yukio; Ohnuma, Mitsuru; Ishiyama, Akihiko; Ishii, Tetsuko; Nakamura, Yoshiyuki; Horigome, Hitoshi; Chiba, Toshio

    2008-03-01

    We developed a fetal magnetocardiography (fMCG) system that uses a pair of two-dimensional gradiometers to achieve high signal-to-noise ratio. The gradiometer, which is based on a low-Tc superconducting quantum interference device, detects the gradient of a magnetic field in two orthogonal directions. Gradiometer position is easy to adjust by operating the gantry to drive the cryostat in both the swinging and axial directions. As a result, a fMCG waveform for 25weeks' gestation was measured under an unshielded environment in real time. Moreover, the P and T waves for 25 and 34weeks' gestation, respectively, were obtained by averaging. These results indicate that this two-dimensional gradiometer is one of the most promising techniques for measuring fetal heart rate and diagnosing fetal arrhythmia.

  9. Commercialization and Industrial Development for the Fetal Hear Rate Monitor

    NASA Technical Reports Server (NTRS)

    Zahorian, Stephen

    2000-01-01

    The primary objectives for this task were to continue the development and testing of the NASA/ODU passive acoustic fetal heart rate monitor, with the goal of transferring the technology to the commercial sector. Areas of work included: 1. To assist in the development of a new hardware front end electronics box for the fetal heart rate monitor, so as to reduce the size of the electronics box, and also to provide for a "low-frequency" and "high-frequency" mode of operation. To make necessary changes in the operating software to support the two modes of operation. 2. To provide an option for a strip chart recording for the system, so that medical personnel could more easily make comparisons with ultra sound strip chart recordings. and 3. To help with continued testing of the system.

  10. [Interest of lactate micro-dosage in scalp and umbilical cord in cases of abnormal fetal heart rate during labor. Prospective study on 162 patients].

    PubMed

    Paris, A; Maurice-Tison, S; Coatleven, F; Vandenbossche, F; Dallay, D; Horovitz, J

    2012-06-01

    To compare the interest of lactate microanalysis with pH measurement (Gold Standard procedure) in cord blood and fetal scalp blood samples for the assessment of abnormal fetal heart rate (FHR) during labour. A prospective observational study conducted from July 1st 2007 till March 31st 2008 on 162 patients with abnormal FHR during labour. Sampling failure for scalp lactate was less than 1 % compared to a failure of 10.5 % for scalp pH (P<0.001). There was a good correlation between pH and lactates in fetal scalp blood samples and in cord blood samples, between lactate in the last fetal scalp sample and in cord blood. When there was umbilical acidosis (pH≤7.15 or lactate≥5mmol/L), Apgar score at 5 minutes was significantly lower than when there was no acidosis (4.66±3.59 versus 8.35±2.73 for pH ; 6.6±3.77 versus 8.45±2.58 for lactate). The specificity of the lactate in the umbilical cord artery (≥5 mmol/laws) was 76.4 % for predicting an Apgar score at 5 minutes less than 7 ; 79.7 % for predicting the need for immediate neonatal care ; 77.3 % for predicting an hospital stay in neonatal unit. These figures were generally worse but close to those found for a threshold value of umbilical artery pH≤7.15. The values of lactate in cord blood and fetal scalp blood samples were comparable to pH values (Gold standard procedure). This method is easy to perform and is an attractive alternative to pH for monitoring fetal asphyxia. It is our opinion that the combination of the two methods is of interest. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  11. Detection of congenital heart defects throughout pregnancy; impact of first trimester ultrasound screening for cardiac abnormalities.

    PubMed

    Eleftheriades, Makarios; Tsapakis, Elsa; Sotiriadis, Alexandros; Manolakos, Emmanouil; Hassiakos, Demetrios; Botsis, Demetrios

    2012-12-01

    To evaluate prospectively the efficacy to screen for congenital heart defects (CHD) during the first trimester nuchal translucency (NT) ultrasound examination by assessing the four chambers' view of fetal heart. Pregnancies that were examined prospectively by ultrasound in the first trimester (11th-14th week), the second (19th-24th week) and third trimester were included in the study. 3774 fetuses were examined and fetal heart was assessed during the NT scan by examining the four chambers view. Detailed echocardiography was performed during the anomaly and growth scans. Diagnosis of congenital heart defects (CHD) was further confirmed by a fetal cardiologist. The four chambers view was obtained in 99.52% of the cases. CHD were diagnosed in 29 fetuses (0.77%). Thirteen cases (44.8%) were detected during the 11-13 weeks' scan, 14 cases (48.3%) during the anomaly scan, 1 CHD (3.5%) during the third trimester scan and 1 case (3.5%) postpartum. Assessment of the four chambers of fetal heart early in pregnancy was feasible and allowed the detection of 45% of CHD. Additional parameters of fetal cardiac anatomy during the NT scan may further improve the detection rate providing pregnancy management information early in the first trimester.

  12. Maturation of the developing human fetal prostate in a rodent xenograft model

    PubMed Central

    Saffarini, Camelia M.; McDonnell, Elizabeth V.; Amin, Ali; Spade, Daniel J.; Huse, Susan M.; Kostadinov, Stefan; Hall, Susan J.; Boekelheide, Kim

    2015-01-01

    Background Prostate cancer is the most commonly diagnosed non-skin cancer in men. The etiology of prostate cancer is unknown, although both animal and epidemiologic data suggest that early life exposures to various toxicants, may impact DNA methylation status during development, playing an important role. Methods We have developed a xenograft model to characterize the growth and differentiation of human fetal prostate implants (gestational age 12-24 weeks) that can provide new data on the potential role of early life stressors on prostate cancer. The expression of key immunohistochemical markers responsible for prostate maturation was evaluated, including p63, cytokeratin 18, α-smooth muscle actin, vimentin, caldesmon, Ki-67, prostate specific antigen, estrogen receptor-α, and androgen receptor. Xenografts were separated into epithelial and stromal compartments using laser capture microdissection (LCM), and the DNA methylation status was assessed in >480,000 CpG sites throughout the genome. Results Xenografts demonstrated growth and maturation throughout the 200 days of post-implantation evaluation. DNA methylation profiles of laser capture micro-dissected tissue demonstrated tissue-specific markers clustered by their location in either the epithelium or stroma of human prostate tissue. Differential methylated promoter region CpG-associated gene analysis revealed significantly more stromal than epithelial DNA methylation in the 30 and 90-day xenografts. Functional classification analysis identified CpG-related gene clusters in methylated epithelial and stromal human xenografts. Conclusion This study of human fetal prostate tissue establishes a xenograft model that demonstrates dynamic growth and maturation, allowing for future mechanistic studies of the developmental origins of later life proliferative prostate disease. PMID:24038131

  13. Comparative study of teratogenic potentials of crude ethanolic root bark and leaf extract of Rauwolfia vomitoria (apocynaceae) on the fetal heart

    PubMed Central

    Eluwa, Mokutima A.; Udoaffah, Matilda T.; Vulley, Moses B. G.; Ekanem, Theresa B.; Akpantah, Amabe O.; Asuquo, Olaitan A.; Ekong, Moses B.

    2010-01-01

    Background: Rauwolfia vomitoria, a tropical shrub, is a medicinal plant used in the treatment of a variety of ailments. It is popular to the locals because of its anti-hypertensive and sedative properties. Aim: This is to find the probable teratogenic effects of ethanolic leaf and root bark extracts of Rauwolfia vomitoria on the morphological and histological features of the fetal heart. Material and Methods: Twenty five female rats weighing between 170-200g were used for this study. The rats were divided into five groups labeled A, B, C, D and E, with each group consisting of five rats. Pregnancy was induced by caging the female rats with sexually matured males. The presence of vaginal plug and tail structures in the vaginal smear the following morning confirmed coition, and it was regarded as day 0 of pregnancy. Group A was given sham treatment of distilled water. Group B and C received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic leaf extract of Rauwolfia vomitoria, and those in groups D and E received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic root bark extract of Rauwolfia vomitoria. These treatments were on days 7-11 of gestation (5 days) with the aid of an orogastric tube. On the day 20 of gestation, the rats were sacrificed and the fetuses examined for gross anomalies, preserved and latter process for histological studies. Results: There were no mortality in this study, and no obvious gross malformations in the fetuses. Histological observations of the fetal heart showed marked distortion of the cardiac muscle nuclei and myocardial fibers in the treated groups particularly those whose mothers received 250mg/kg of the extracts. These effects were more pronounced in the groups whose mothers received the root extract when compared with the control and the groups whose mothers received the leaf extract. Conclusion: This result suggests that high doses of ethanolic leaf and root extracts of Rauwolfia vomitoria may be

  14. Comparative study of teratogenic potentials of crude ethanolic root bark and leaf extract of Rauwolfia vomitoria (apocynaceae) on the fetal heart.

    PubMed

    Eluwa, Mokutima A; Udoaffah, Matilda T; Vulley, Moses B G; Ekanem, Theresa B; Akpantah, Amabe O; Asuquo, Olaitan A; Ekong, Moses B

    2010-12-01

    Rauwolfia vomitoria, a tropical shrub, is a medicinal plant used in the treatment of a variety of ailments. It is popular to the locals because of its anti-hypertensive and sedative properties. This is to find the probable teratogenic effects of ethanolic leaf and root bark extracts of Rauwolfia vomitoria on the morphological and histological features of the fetal heart. Twenty five female rats weighing between 170-200g were used for this study. The rats were divided into five groups labeled A, B, C, D and E, with each group consisting of five rats. Pregnancy was induced by caging the female rats with sexually matured males. The presence of vaginal plug and tail structures in the vaginal smear the following morning confirmed coition, and it was regarded as day 0 of pregnancy. Group A was given sham treatment of distilled water. Group B and C received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic leaf extract of Rauwolfia vomitoria, and those in groups D and E received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic root bark extract of Rauwolfia vomitoria. These treatments were on days 7-11 of gestation (5 days) with the aid of an orogastric tube. On the day 20 of gestation, the rats were sacrificed and the fetuses examined for gross anomalies, preserved and latter process for histological studies. There were no mortality in this study, and no obvious gross malformations in the fetuses. Histological observations of the fetal heart showed marked distortion of the cardiac muscle nuclei and myocardial fibers in the treated groups particularly those whose mothers received 250mg/kg of the extracts. These effects were more pronounced in the groups whose mothers received the root extract when compared with the control and the groups whose mothers received the leaf extract. This result suggests that high doses of ethanolic leaf and root extracts of Rauwolfia vomitoria may be cardiotoxic to the developing rat's heart.

  15. Alternative Splicing of NOX4 in the Failing Human Heart

    PubMed Central

    Varga, Zoltán V.; Pipicz, Márton; Baán, Júlia A.; Baranyai, Tamás; Koncsos, Gábor; Leszek, Przemyslaw; Kuśmierczyk, Mariusz; Sánchez-Cabo, Fátima; García-Pavía, Pablo; Brenner, Gábor J.; Giricz, Zoltán; Csont, Tamás; Mendler, Luca; Lara-Pezzi, Enrique; Pacher, Pál; Ferdinandy, Péter

    2017-01-01

    Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions) were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation. Deep RNA sequencing of the cardiac transcriptome indicated extensive alternative splicing of the NOX4 gene in heart failure as compared to samples from healthy donor hearts. Long distance PCR analysis with a universal 5′-3′ end primer pair, allowing amplification of different splice variants, confirmed the presence of the splice variants. To assess translation of the alternatively spliced transcripts we determined protein expression of NOX4 by using a specific antibody recognizing a conserved region in all variants. Western blot analysis showed up-regulation of the full-length NOX4 in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms both in control and failing samples with disease-associated expression pattern. We describe here for the first time that NOX4 undergoes extensive alternative splicing in human hearts which gives rise to the expression of different enzyme isoforms. The full length NOX4 is significantly upregulated in ischemic cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure. PMID:29204124

  16. Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

    PubMed Central

    Hiby, Susan E.; Apps, Richard; Sharkey, Andrew M.; Farrell, Lydia E.; Gardner, Lucy; Mulder, Arend; Claas, Frans H.; Walker, James J.; Redman, Christopher C.; Morgan, Linda; Tower, Clare; Regan, Lesley; Moore, Gudrun E.; Carrington, Mary; Moffett, Ashley

    2010-01-01

    Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells — specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells — influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2+ trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success. PMID:20972337

  17. Human heart conjugate cooling simulation: Unsteady thermo-fluid-stress analysis

    PubMed Central

    Abdoli, Abas; Dulikravich, George S.; Bajaj, Chandrajit; Stowe, David F.; Jahania, M. Salik

    2015-01-01

    The main objective of this work was to demonstrate computationally that realistic human hearts can be cooled much faster by performing conjugate heat transfer consisting of pumping a cold liquid through the cardiac chambers and major veins while keeping the heart submerged in cold gelatin filling a cooling container. The human heart geometry used for simulations was obtained from three-dimensional, high resolution MRI scans. Two fluid flow domains for the right (pulmonic) and left (systemic) heart circulations, and two solid domains for the heart tissue and gelatin solution were defined for multi-domain numerical simulation. Detailed unsteady temperature fields within the heart tissue were calculated during the conjugate cooling process. A linear thermoelasticity analysis was performed to assess the stresses applied on the heart due to the coolant fluid shear and normal forces and to examine the thermal stress caused by temperature variation inside the heart. It was demonstrated that a conjugate cooling effort with coolant temperature at +4°C is capable of reducing the average heart temperature from +37°C to +8°C in 25 minutes for cases in which the coolant was steadily pumped only through major heart inlet veins and cavities. PMID:25045006

  18. Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep.

    PubMed

    Wang, Qiming; Gold, Nathan; Frasch, Martin G; Huang, Huaxiong; Thiriet, Marc; Wang, Xiaogang

    2015-12-01

    Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation.

  19. Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.

    PubMed

    Santos, Marta; Bastos, Pedro; Gonzaga, Silvia; Roriz, José-Mário; Baptista, Maria J; Nogueira-Silva, Cristina; Melo-Rocha, Gustavo; Henriques-Coelho, Tiago; Roncon-Albuquerque, Roberto; Leite-Moreira, Adelino F; De Krijger, Ronald R; Tibboel, Dick; Rottier, Robbert; Correia-Pinto, Jorge

    2006-04-01

    Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.

  20. Handheld fetal Doppler device for assessing heart rate in neonatal resuscitation.

    PubMed

    Shimabukuro, Rinshu; Takase, Kozo; Ohde, Sachiko; Kusakawa, Isao

    2017-10-01

    The use of neonatal three-lead electrocardiograms (Neo-ECG) is suggested for the assessment of heart rate (HR) in neonatal resuscitation, but primary childbirth facilities (i.e. maternity clinics or maternity homes) are not sufficiently equipped for this. The aim of this study was to therefore to confirm the potential of a handheld fetal Doppler device (FDD), widely used to assess HR in labor room resuscitation, and to compare its equivalency to Neo-ECG. In low-risk full-term infants, HR was measured five times per minute in minutes 1-5 after delivery using the FDD and Neo-ECG, and their equivalence compared. The equivalence margin was set at a HR difference of <±5 beats/min and <±5%. Moreover, the times at which HR was displayed were measured for both methods. FDD and Neo-ECG HR correlated strongly (r = 0.977) in 155 measurements in 33 cases. The mean HR difference was -0.123 beats/min (95%CI: -0.594 to +0.345), and the logarithmic transformation of the HR ratio was -0.0003 (95%CI: -0.0020 to +0.0015). The mean HR difference and HR ratio were within the equivalence margin. For HR assessment using the FDD, 155 of 165 measurements (93.9%) could be obtained in <10 s. In HR assessment, FDD is a valid substitute for Neo-ECG in primary childbirth facilities that are not sufficiently equipped for Neo-ECG. © 2017 Japan Pediatric Society.

  1. Passive fetal monitoring sensor

    NASA Astrophysics Data System (ADS)

    Zuckerwar, Allan J.; Hall, Earl T.; Baker, Donald A.; Bryant, Timothy D.

    1992-08-01

    An ambulatory, passive sensor for use in a fetal monitoring system is discussed. The invention is comprised of a piezoelectric polymer film, combined with a metallic mounting plate fastened to a belt, and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted by a fetus inside an expectant mother. Additionally, the monitor will filter out pressure pulses arising from other sources, such as the maternal heart.

  2. Passive fetal monitoring sensor

    NASA Astrophysics Data System (ADS)

    1990-07-01

    The invention is an ambulatory, passive sensor for use in a fetal monitoring system. The invention incorporates piezoelectric polymer film combined with a metallic mounting plate fastened to a belt and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted from a fetus inside an expectant mother and to provide means for filtering out pressure pulses arising from other sources, such as the maternal heart.

  3. Passive fetal monitoring sensor

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J. (Inventor); Hall, Earl T. (Inventor); Baker, Donald A. (Inventor); Bryant, Timothy D. (Inventor)

    1992-01-01

    An ambulatory, passive sensor for use in a fetal monitoring system is discussed. The invention is comprised of a piezoelectric polymer film, combined with a metallic mounting plate fastened to a belt, and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted by a fetus inside an expectant mother. Additionally, the monitor will filter out pressure pulses arising from other sources, such as the maternal heart.

  4. Antepartum fetal heart rate feature extraction and classification using empirical mode decomposition and support vector machine

    PubMed Central

    2011-01-01

    Background Cardiotocography (CTG) is the most widely used tool for fetal surveillance. The visual analysis of fetal heart rate (FHR) traces largely depends on the expertise and experience of the clinician involved. Several approaches have been proposed for the effective interpretation of FHR. In this paper, a new approach for FHR feature extraction based on empirical mode decomposition (EMD) is proposed, which was used along with support vector machine (SVM) for the classification of FHR recordings as 'normal' or 'at risk'. Methods The FHR were recorded from 15 subjects at a sampling rate of 4 Hz and a dataset consisting of 90 randomly selected records of 20 minutes duration was formed from these. All records were labelled as 'normal' or 'at risk' by two experienced obstetricians. A training set was formed by 60 records, the remaining 30 left as the testing set. The standard deviations of the EMD components are input as features to a support vector machine (SVM) to classify FHR samples. Results For the training set, a five-fold cross validation test resulted in an accuracy of 86% whereas the overall geometric mean of sensitivity and specificity was 94.8%. The Kappa value for the training set was .923. Application of the proposed method to the testing set (30 records) resulted in a geometric mean of 81.5%. The Kappa value for the testing set was .684. Conclusions Based on the overall performance of the system it can be stated that the proposed methodology is a promising new approach for the feature extraction and classification of FHR signals. PMID:21244712

  5. Fetal Cardiac Responding: A Correlate of Birth Weight and Neonatal Behavior.

    ERIC Educational Resources Information Center

    Emory, Eugene K.; Noonan, John R.

    1984-01-01

    Explores whether an empirical classification of healthy fetuses as fetal heart rate accelerators or decelerators would predict birth weight and neonatal behavior scored with the Brazelton Neonatal Behavior Assessment Scale. (Author/RH)

  6. Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum.

    PubMed

    Vasung, L; Jovanov-Milošević, N; Pletikos, M; Mori, S; Judaš, M; Kostović, Ivica

    2011-01-01

    Periventricular pathway (PVP) system of the developing human cerebrum is situated medial to the intermediate zone in the close proximity to proliferative cell compartments. In order to elucidate chemical properties and developing trajectories of the PVP we used DTI in combination with acetylcholinesterase histochemistry, SNAP-25 immunocytochemistry and axonal cytoskeletal markers (SMI312, MAP1b) immunocytochemistry on postmortem paraformaldehyde-fixed brains of 30 human fetuses ranging in age from 10 to 38 postconceptional weeks (PCW), 2 infants (age 1-3 months) and 1 adult brain. The PVP appears in the early fetal period (10-13 PCW) as two defined fibre bundles: the corpus callosum (CC) and the fetal fronto-occipital fascicle (FOF). In the midfetal period (15-18 PCW), all four components of the PVP can be identified: (1) the CC, which at rostral levels forms a voluminous callosal plate; (2) the FOF, with SNAP-25-positive fibers; (3) the fronto-pontine pathway (FPP) which for a short distance runs within the PVP; and (4) the subcallosal fascicle of Muratoff (SFM) which contains cortico-caudate projections. The PVPs are situated medial to the internal capsule at the level of the cortico-striatal junction; they remain prominent during the late fetal and early preterm period (19-28 PCW) and represent a portion of the wider periventricular crossroad of growing associative, callosal and projection pathways. In the perinatal period, the PVPs change their topographical relationships, decrease in size and the FOF looses its SNAP-25-reactivity. In conclusion, the hitherto undescribed PVP of the human fetal cerebrum contains forerunners of adult associative and projection pathways. Its transient chemical properties and relative exuberance suggest that the PVP may exert influence on the development of cortical connectivity (intermediate targeting) and other neurogenetic events such as neuronal proliferation. The PVP's topographical position also indicates that it is a major

  7. Fetal Programming and Cardiovascular Pathology

    PubMed Central

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  8. Effect of Thrombin on Human Amnion Mesenchymal Cells, Mouse Fetal Membranes, and Preterm Birth*

    PubMed Central

    Mogami, Haruta; Keller, Patrick W.; Shi, Haolin; Word, R. Ann

    2014-01-01

    Here, we investigated the effects of thrombin on matrix metalloproteinases (MMPs) and prostaglandin (PG) synthesis in fetal membranes. Thrombin activity was increased in human amnion from preterm deliveries. Treatment of mesenchymal, but not epithelial, cells with thrombin resulted in increased MMP-1 and MMP-9 mRNA and enzymatic activity. Thrombin also increased COX2 mRNA and PGE2 in these cells. Protease-activated receptor-1 (PAR-1) was localized to amnion mesenchymal and decidual cells. PAR-1-specific inhibitors and activating peptides indicated that thrombin-induced up-regulation of MMP-9 was mediated via PAR-1. In contrast, thrombin-induced up-regulation of MMP-1 and COX-2 was mediated through Toll-like receptor-4, possibly through thrombin-induced release of soluble fetal fibronectin. In vivo, thrombin-injected pregnant mice delivered preterm. Mmp8, Mmp9, and Mmp13, and PGE2 content was increased significantly in fetal membranes from thrombin-injected animals. These results indicate that thrombin acts through multiple mechanisms to activate MMPs and PGE2 synthesis in amnion. PMID:24652285

  9. Quantitative comparison of entropy analysis of fetal heart rate variability related to the different stages of labor.

    PubMed

    Lim, Jongil; Kwon, Ji Young; Song, Juhee; Choi, Hosoon; Shin, Jong Chul; Park, In Yang

    2014-02-01

    The interpretation of the fetal heart rate (FHR) signal considering labor progression may improve perinatal morbidity and mortality. However, there have been few studies that evaluate the fetus in each labor stage quantitatively. To evaluate whether the entropy indices of FHR are different according to labor progression. A retrospective comparative study of FHR recordings in three groups: 280 recordings in the second stage of labor before vaginal delivery, 31 recordings in the first stage of labor before emergency cesarean delivery, and 23 recordings in the pre-labor before elective cesarean delivery. The stored FHR recordings of external cardiotocography during labor. Approximate entropy (ApEn) and sample entropy (SampEn) for the final 2000 RR intervals. The median ApEn and SampEn for the 2000 RR intervals showed the lowest values in the second stage of labor, followed by the emergency cesarean group and the elective cesarean group for all time segments (all P<0.001). Also, in the second stage of labor, the final 5 min of 2000 RR intervals had a significantly lower median ApEn (0.49 vs. 0.44, P=0.001) and lower median SampEn (0.34 vs. 0.29, P<0.001) than the initial 5 min of 2000 RR intervals. Entropy indices of FHR were significantly different according to labor progression. This result supports the necessity of considering labor progression when developing intrapartum fetal monitoring using the entropy indices of FHR. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure.

    PubMed

    Vegter, Eline L; Ovchinnikova, Ekaterina S; Silljé, Herman H W; Meems, Laura M G; van der Pol, Atze; van der Velde, A Rogier; Berezikov, Eugene; Voors, Adriaan A; de Boer, Rudolf A; van der Meer, Peter

    2017-01-01

    We recently identified a set of plasma microRNAs (miRNAs) that are downregulated in patients with heart failure in comparison with control subjects. To better understand their meaning and function, we sought to validate these circulating miRNAs in 3 different well-established rat and mouse heart failure models, and correlated the miRNAs to parameters of cardiac function. The previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-199a-3p, miR-223-3p, miR-423-3p, miR-423-5p and miR-652-3p were measured by means of quantitative real time polymerase chain reaction (qRT-PCR) in plasma samples of 8 homozygous TGR(mREN2)27 (Ren2) transgenic rats and 8 (control) Sprague-Dawley rats, 6 mice with angiotensin II-induced heart failure (AngII) and 6 control mice, and 8 mice with ischemic heart failure and 6 controls. Circulating miRNA levels were compared between the heart failure animals and healthy controls. Ren2 rats, AngII mice and mice with ischemic heart failure showed clear signs of heart failure, exemplified by increased left ventricular and lung weights, elevated end-diastolic left ventricular pressures, increased expression of cardiac stress markers and reduced left ventricular ejection fraction. All miRNAs were detectable in plasma from rats and mice. No significant differences were observed between the circulating miRNAs in heart failure animals when compared to the healthy controls (all P>0.05) and no robust associations with cardiac function could be found. The previous observation that miRNAs circulate in lower levels in human patients with heart failure could not be validated in well-established rat and mouse heart failure models. These results question the translation of data on human circulating miRNA levels to experimental models, and vice versa the validity of experimental miRNA data for human heart failure.

  11. Isolation and expression of the human gametocyte-specific factor 1 gene (GTSF1) in fetal ovary, oocytes, and preimplantation embryos.

    PubMed

    Huntriss, John; Lu, Jianping; Hemmings, Karen; Bayne, Rosemary; Anderson, Richard; Rutherford, Anthony; Balen, Adam; Elder, Kay; Picton, Helen M

    2017-01-01

    Gametocyte-specific factor 1 has been shown in other species to be required for the silencing of retrotransposons via the Piwi-interacting RNA (piRNA) pathway. In this study, we aimed to isolate and assess expression of transcripts of the gametocyte-specific factor 1 (GTSF1) gene in the human female germline and in preimplantation embryos. Complementary DNA (cDNA) libraries from human fetal ovaries and testes, human oocytes and preimplantation embryos and ovarian follicles isolated from an adult ovarian cortex biopsy were used to as templates for PCR, cloning and sequencing, and real time PCR experiments of GTSF1 expression. GTSF1 cDNA clones that covered the entire coding region were isolated from human oocytes and preimplantation embryos. GTSF1 mRNA expression was detected in archived cDNAs from staged human ovarian follicles, germinal vesicle (GV) stage oocytes, metaphase II oocytes, and morula and blastocyst stage preimplantation embryos. Within the adult female germline, expression was highest in GV oocytes. GTSF1 mRNA expression was also assessed in human fetal ovary and was observed to increase during gestation, from 8 to 21 weeks, during which time oogonia enter meiosis and primordial follicle formation first occurs. In human fetal testis, GTSF1 expression also increased from 8 to 19 weeks. To our knowledge, this report is the first to describe the expression of the human GTSF1 gene in human gametes and preimplantation embryos.

  12. Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries.

    PubMed

    Chai, M; Barker, G; Menon, R; Lappas, M

    2012-08-01

    Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Maturation of Fetal Responses to Music

    ERIC Educational Resources Information Center

    Kisilevsky, B. S.; Hains, S. M. J.; Jacquet, A.-Y.; Granier-Deferre, C.; Lecanuet, J. P.

    2004-01-01

    Maturation of fetal response to music was characterized over the last trimester of pregnancy using a 5-minute piano recording of Brahms' Lullaby, played at an average of 95, 100, 105 or 110 dB (A). Within 30 seconds of the onset of the music, the youngest fetuses (28-32 weeks GA) showed a heart rate increase limited to the two highest dB levels;…

  14. Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves.

    PubMed

    Peña-Silva, Ricardo A; Miller, Jordan D; Chu, Yi; Heistad, Donald D

    2009-10-01

    Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2*.-) was measured in heart valves from explanted human hearts that were not used for transplantation. (O2*.-) levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in (O2*.-). Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased (O2*.-) levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in (O2*.-) during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated (O2*.-), and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.

  15. Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

    PubMed

    Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

    2015-12-01

    Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

  16. Fetal circulatory responses to oxygen lack.

    PubMed

    Jensen, A; Berger, R

    1991-10-01

    The knowledge on fetal and neonatal circulatory physiology accumulated by basic scientists and clinicians over the years has contributed considerably to the recent decline of perinatal morbidity and mortality. This review will summarize the peculiarities of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during oxygen lack caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organs will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxemia and asphyxia is a centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory decentralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia.

  17. Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection

    PubMed Central

    Lloyd, David F.A.; Price, Anthony N.; Kuklisova Murgasova, Maria; Aljabar, Paul; Malik, Shaihan J.; Lohezic, Maelene; Rutherford, Mary A.; Pushparajah, Kuberan; Razavi, Reza; Hajnal, Joseph V.

    2017-01-01

    Purpose Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion. Methods The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image‐based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user‐defined region of interest delineating the fetal heart. The method was evaluated in 30 mid‐ to late gestational age singleton pregnancies scanned without maternal breath‐hold. Results The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact‐free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets. Conclusions The proposed method shows promise as a motion‐tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image‐space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med 79:327–338, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:28370252

  18. Cold-perfusion decellularization of whole-organ porcine pancreas supports human fetal pancreatic cell attachment and expression of endocrine and exocrine markers

    PubMed Central

    Elebring, Erik; Kuna, Vijay K; Kvarnström, Niclas; Sumitran-Holgersson, Suchitra

    2017-01-01

    Despite progress in the field of decellularization and recellularization, the outcome for pancreas has not been adequate. This might be due to the challenging dual nature of pancreas with both endocrine and exocrine tissues. We aimed to develop a novel and efficient cold-perfusion method for decellularization of porcine pancreas and recellularize acellular scaffolds with human fetal pancreatic stem cells. Decellularization of whole porcine pancreas at 4°C with sodium deoxycholate, Triton X-100 and DNase efficiently removed cellular material, while preserving the extracellular matrix structure. Furthermore, recellularization of acellular pieces with human fetal pancreatic stem cells for 14 days showed attached and proliferating cells. Both endocrine (C-peptide and PDX1) and exocrine (glucagon and α-amylase) markers were expressed in recellularized tissues. Thus, cold-perfusion can successfully decellularize porcine pancreas, which when recellularized with human fetal pancreatic stem cells shows relevant endocrine and exocrine phenotypes. Decellularized pancreas is a promising biomaterial and might translate to clinical relevance for treatment of diabetes. PMID:29118967

  19. 2D/3D fetal cardiac dataset segmentation using a deformable model.

    PubMed

    Dindoyal, Irving; Lambrou, Tryphon; Deng, Jing; Todd-Pokropek, Andrew

    2011-07-01

    To segment the fetal heart in order to facilitate the 3D assessment of the cardiac function and structure. Ultrasound acquisition typically results in drop-out artifacts of the chamber walls. The authors outline a level set deformable model to automatically delineate the small fetal cardiac chambers. The level set is penalized from growing into an adjacent cardiac compartment using a novel collision detection term. The region based model allows simultaneous segmentation of all four cardiac chambers from a user defined seed point placed in each chamber. The segmented boundaries are automatically penalized from intersecting at walls with signal dropout. Root mean square errors of the perpendicular distances between the algorithm's delineation and manual tracings are within 2 mm which is less than 10% of the length of a typical fetal heart. The ejection fractions were determined from the 3D datasets. We validate the algorithm using a physical phantom and obtain volumes that are comparable to those from physically determined means. The algorithm segments volumes with an error of within 13% as determined using a physical phantom. Our original work in fetal cardiac segmentation compares automatic and manual tracings to a physical phantom and also measures inter observer variation.

  20. Aquaporin 3 expression in human fetal membranes and its up-regulation by cyclic adenosine monophosphate in amnion epithelial cell culture.

    PubMed

    Wang, Shengbiao; Amidi, Fataneh; Beall, Marie; Gui, Lizhen; Ross, Michael G

    2006-04-01

    The cell membrane water channel protein aquaporins (AQPs) may be important in regulating the intramembranous (IM) pathway of amniotic fluid (AF) resorption. The objective of the present study was to determine whether aquaporin 3 (AQP3) is expressed in human fetal membranes and to further determine if AQP3 expression in primary human amnion cell culture is regulated by second-messenger cyclic adenosine monophosphate (cAMP). AQP3 expression in human fetal membranes of normal term pregnancy was studied by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). To determine the effect of cAMP on AQP3 expression, primary human amnion cell cultures were treated in either heat-inactivated medium alone (control), or heat-inactivated medium containing: (1) SP-cAMP, a membrane-permeable and phosphodiesterase resistant cAMP agonist, or (2) forskolin, an adenylate cyclase stimulator. Total RNA was isolated and multiplex real-time RT-PCR employed for relative quantitation of AQP3 expression. We detected AQP3 expression in placenta, chorion, and amnion using RT-PCR. Using IHC, we identified AQP3 protein expression in placenta syncytiotrophoblasts and cytotrophoblasts, chorion cytotrophoblasts, and amnion epithelia. In primary amnion epithelial cell culture, AQP3 mRNA significantly increased at 2 hours following forskolin or SP-cAMP, remained elevated at 10 hours following forskolin, and returned to baseline levels by 20 hours following treatment. This study provides evidence of AQP3 expression in human fetal membranes and demonstrates that AQP3 expression in primary human amnion cell culture is up-regulated by second-messenger cAMP. As AQP3 is permeable to water, urea, and glycerol, modulation of its expression in fetal membranes may contribute to AF homeostasis.