Foetal heart rate power spectrum response to uterine contraction

Cardiotocography is the most diffused prenatal diagnostic technique in clinical routine. The simultaneous recording of foetal heart rate (FHR) and uterine contractions (UC) provides useful information about foetal well-being during pregnancy and labour. However, foetal electronic monitoring interpretation still lacks reproducibility and objectivity. New methods of interpretation and new parameters can further support physicians’ decisions. Besides common time-domain analysis, study of the variability of FHR can potentially reveal autonomic nervous system activity of the foetus. In particular, it is clinically relevant to investigate foetal reactions to UC to diagnose foetal distress early. Uterine contraction being a strong stimulus for the foetus and its autonomic nervous system, it is worth exploring the FHR variability response. This study aims to analyse modifications of the power spectrum of FHR variability corresponding to UC. Cardiotocographic signal tracts corresponding to 127 UC relative to 30 healthy foetuses were analysed. Results mainly show a general, statistically significant (t test, p<0.01) power increase of the FHR variability in the LF 0.03–0.2 Hz and HF 0.2–1 in correspondence of the contraction with respect to a reference tract set before contraction onset. Time evolution of the power within these bands was computed by means of time-varying spectral estimation to concisely show the FHR response along a uterine contraction. A synchronised grand average of these responses was also computed to verify repeatability, using the contraction apex as time reference. Such modifications of the foetal HRV that follow a contraction can be a sign of ANS reaction and, therefore, additional, objective information about foetal reactivity during labour.     

Comparison of real beat-to-beat signals with commercially available 4 Hz sampling on the evaluation of foetal heart rate variability

Evaluation of foetal heart rate (FHR) variability is an essential part of foetal monitoring, but a precise quantification of this parameter depends on the quality of the signal. In this study, we compared real FHR beat-to-beat signals with 4 Hz sampling provided by commercial foetal monitors on linear and nonlinear indices and analysed their clinical implications. Simultaneous acquisition of beat-to-beat signals and their 4 Hz sampling rate counterparts was performed using a scalp electrode, during the last hour of labour in 21 fetuses born with an umbilical artery blood (UAB) pH ≥ 7.20 and 6 born with an UAB pH < 7.20. For each case, the first and last 10 min segments were analysed, using time and frequency domain linear, and nonlinear FHR indices, namely mean FHR, low frequency, high frequency, approximate, sample and multiscale entropy. Significant differences in variability indices were found between beat-to-beat and 4 Hz sampled signals, with a lesser effect seen with 2 Hz sampling. These differences did not affect physiological changes observed during labour progression, such as decreased entropy and linear time domain indices, and increased frequency domain indices. However, significant differences were found in the discrimination between fetuses born with different UAB pHs, with beat-to-beat sampling providing better results in linear indices and 4 Hz sampling better results in entropy indices. In conclusion, different FHR sampling frequencies can significantly affect the quantification of variability indices. This needs to be taken into account in the interpretation of FHR variability and in the development of new equipment.     

Serum mannose–binding lectin (MBL) concentrations are reduced in non-pregnant women with previous adverse pregnancy outcomes

Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%-97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%-83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%-83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.     

Simultaneity of foetal heart rate acceleration and foetal trunk movement determined by foetal magnetocardiogram actocardiography

We describe a new method of actocardiography, foetal magnetocardiogram (fMCG) actocardiography, which is based on the high sensitivity of the fMCG to foetal trunk movements. We demonstrate the efficacy of the method by applying it to assess the simultaneity of onset of foetal heart rate (FHR) acceleration and foetal trunk movement. The analysis was restricted to events for which the onset of FHR accelerations and foetal movements could be determined accurately, i.e. when FHR was stable and near the average quiescent level just prior to the acceleration. We found that FHR accelerations coincided with or preceded foetal movements nearly all the time. This supports the hypothesis of coordinated control of FHR accelerations and foetal movements more strongly than prior studies, based on other techniques. We also found that beat-to-beat FHR variability often decreased at or near the start of FHR accelerations and that this occurrence was an accurate marker of foetal movement onset, even when foetal movement onset lagged FHR accelerations.     

Relation of fetal heart rate signals with unassignable baseline to poor neonatal state at birth

Electronic fetal heart rates (FHR) are used to monitor fetal health during labour. The paper records are visually assessed by clinicians, but automated alternatives are being developed. Interpretation, visual or computerised, depends on assigning a baseline to identify key features such as accelerations and decelerations. However, when the FHR is unstable the baseline may be unassignable, making conventional analysis unreliable. Such instability may reflect on fetal health. If true, these segments should not be discarded but quantified, for which we have developed a numerical method. In 7,568 labours, the association between unassignable baseline and umbilical arterial blood pH ≤ 7.05 at birth (evidence of poor health) was studied retrospectively. We found a consistent increase of the risk for acidaemia with longer intervals of unassignable baseline. This is detectable at the end of the first stage of labour, but stronger at the end of the second stage: in the last 30 min of labour, the odds ratios (with respect to baseline assignable throughout this period) increased from 1.99 (15 min unassignable) to 4.9 (30 min unassignable). Computerised analysis of the FHR becomes unreliable when the baseline cannot be assigned; however, this pattern is itself a pathological feature associated with acidaemia at birth.     

Intramyocellular oxygenation during ischemic muscle contractions in vivo

There is some evidence that the fall in intramyocellular oxygen content during ischemic contractions is less than during ischemia alone. We used proton magnetic resonance spectroscopy to determine whether peak deoxy-myoglobin (dMb) obtained during ischemic ankle dorsiflexion contractions attained the maximal dMb level observed during a separate trial of ischemia alone (resting max). In six healthy young men, the rate of myoglobin desaturation was rapid at the onset of ischemic contractions and then slowed as contractions continued, attaining only 75 ± 3.3% (mean ± SE) of resting max dMb by the end of contractions (p = 0.03). Myoglobin continued to desaturate while ischemia was maintained following contractions, reaching 98 ± 1.8% of resting max within 10 min (p = 0.03 vs. end of contractions). Notably, contractions performed after 10 min of ischemia did not affect dMb (dMb = 100 ± 1.5% of resting max, p > 0.99), suggesting that full desaturation had already been achieved. The blunting of desaturation during ischemic contractions is likely a result of slowed mitochondrial oxygen consumption due to limited oxygen availability.     

Nuclear expression of β‐catenin in endometrial hyperplasia as marker of premalignancy

We aimed to assess (1)‐whether nuclear β‐catenin is a marker of endometrial precancer, and (2)‐the diagnostic accuracy of β‐catenin immunohistochemistry in the differential diagnosis between benign and premalignant endometrial hyperplasia (EH), defining criteria for its use. Electronic databases were searched for studies evaluating β‐catenin immunohistochemistry in normal endometrium (NE), benign and/or premalignant EH, and endometrioid carcinoma (EC). Odds ratio (OR; p < 0.05), sensitivity, specificity, diagnostic OR (DOR), positive and negative likelihood ratios (LR+, LR?) were calculated. Subgroup analyses were based on the classification system used (WHO or EIN) and criteria to define aberrant β‐catenin expression (only nuclear or cytoplasmic/nuclear). Twelve studies with 1510 specimens were included. Nuclear β‐catenin rate significantly increased from NE to benign EH (OR = 26.01; p = 0.0002, only in WHO subgroup), and from benign EH to premalignant EH (OR = 3.89; p = 0.0002; more markedly in EIN subgroup), but not from premalignant EH to EC (OR = 0.78; p = 0.29). Nuclear β‐catenin accuracy was very low in WHO subgroup (sensitivity = 0.40, specificity = 0.76, LR+ = 1.85, LR? = 0.72; DOR = 2.89) and moderate in EIN subgroup (sensitivity = 0.19, specificity = 1.00, LR+ = 14.80, LR? = 0.83; DOR = 18.14). Cytoplasmic/nuclear β‐catenin accuracy was absent in WHO subgroup (sensitivity = 0.45, specificity = 0.54, LR+ = 1.01, LR? = 1.01; DOR = 0.99) and low in EIN subgroup (sensitivity = 0.57, specificity = 0.86, LR+ = 3.63, LR? = 0.51; DOR = 8.30). Considering nuclear expression and using EIN system, β‐catenin immunohistochemistry might be reliable as rule‐in test for diagnosis of endometrial precancer, with perfect specificity and moderate overall accuracy.     

Classification of foetal heart rate sequences based on fractal features

Visual inspection of foetal heart rate (FHR) sequences is an important means of foetal well-being evaluation. The application of fractal features for classifying physiologically relevant FHR sequence patterns is reported. The use of fractal features is motivated by the difficulties exhibited by traditional classification schemes to discriminate some classes of FHR sequence and by the recognition that this type of signal exhibits features on different scales of observation, just as fractal signals do. To characterise the signals by fractal features, two approaches are taken. The first models the FHR sequences as temporal fractals. The second uses techniques from the chaos-theory field and aims to model the attractor based on FHR sequences. The fractal features determined by both approaches are used to design a Bayesian classification scheme. Classification results for three classes are presented; they are quite satisfactory and illustrate the importance of this type of methodology.     

Complexity analysis of the fetal heart rate variability: early identification of severe intrauterine growth-restricted fetuses

The main goal of this work is to suggest new indices for a correct identification of the intrauterine growth-restricted (IUGR) fetuses on the basis of fetal heart rate (FHR) variability analysis performed in the antepartum period. To this purpose, we analyzed 59 FHR time series recorded in early periods of gestation through a Hewlett Packard 1351A cardiotocograph. Advanced analysis techniques were adopted including the computation of the Lempel Ziv complexity (LZC) index and the multiscale entropy (MSE), that is, the entropy estimation with a multiscale approach. A multiparametric classifier based on k-mean cluster analysis was also performed to separate pathological and normal fetuses. The results show that the proposed LZC and the MSE could be useful to identify the actual IUGRs and to separate them from the physiological fetuses, providing good values of sensitivity and accuracy (Se = 77.8%, Ac = 82.4%).     

Compact long-term recorder for the transabdominal foetal and maternal electrocardiogram

Foetal heart rate (FHR) monitoring is a proven means of assessing foetal health during the antenatal period. Currently, the only widely available instrumentation for producing these data is based on Doppler ultrasound, a technology that is unsuitable for long-term use. For nearly a century, it has been known that the foetal electrocardiogram (FECG) can be detected using electrodes placed on the maternal abdomen. Although these signals suggest an alternative means of FHR derivation, their use has been limited owing to problems of poor signal-to-noise ratio. However, the eminent suitability of the transabdominal FECG for long-term FHR monitoring has suggested that perseverance with the technique would be worthwhile. The paper describes the design, construction and use of a compact, long-term recorder of three channels of 24 h antenatal transabdominal data. Preliminary use of the recorder in around 400 short recording sessions demonstrates that FHR records of equivalent quality to those from Doppler ultrasound-based instruments can be extracted from such data. The success of FHR derivation is, on average, around 65% of the recording period from around 20 weeks gestation (although this figure is reduced from around 28–32 weeks, and the success rates exhibit a wide range when individual subjects are considered). These results demonstrate that the technique offers, not only a means of acquiring long-term FHR data that are problematic to obtain by other means, but also a more patient-friendly alternative to the Doppler ultrasound technique.     

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

AT‐rich interaction domain 1A (ARID1A) is a tumor suppressor protein involved in endometrioid carcinogenesis. The expression of ARID1A may be lost in the premalignant phase. Our aim was to assess ARID1A as: (i) diagnostic marker to differentiate premalignant endometrial hyperplasia (EH) form benign EH; (ii) prognostic marker for the risk of occult cancer in premalignant EH. A systematic review and meta‐analysis were performed by searching electronic databases from their inception to October 2018 for all studies assessing ARID1A in EH by immunohistochemistry. Sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR?), and diagnostic odds ratio (DOR) were calculated for both diagnostic and prognostic accuracy. LR+ > 5, LR? < 0.2, DOR > 25 defined good accuracy; LR+ > 10, LR? < 0.1, DOR > 100 defined excellent accuracy. Seven studies with 467 EH were included. As diagnostic marker, ARID1A showed sensitivity = 0.12, specificity = 0.99, LR+ = 4.34, LR? = 0.85, DOR = 5.12. As prognostic marker for occult cancer, ARID1A showed sensitivity = 0.33, specificity = 0.99, LR+ = 20.70, LR? = 0.49, DOR = 49.59. In conclusion, ARID1A loss is highly specific, but little accurate as diagnostic marker of premalignant EH. Instead, ARID1A loss in premalignant EH is an accurate and almost perfectly specific prognostic marker for coexistent cancer.     

Detecting liver fibrosis using a machine learning‐based approach to the quantification of the heart‐induced deformation in tagged MR images

Liver disease causes millions of deaths per year worldwide, and approximately half of these cases are due to cirrhosis, which is an advanced stage of liver fibrosis that can be accompanied by liver failure and portal hypertension. Early detection of liver fibrosis helps in improving its treatment and prevents its progression to cirrhosis. In this work, we present a novel noninvasive method to detect liver fibrosis from tagged MRI images using a machine learning‐based approach. Specifically, coronal and sagittal tagged MRI imaging are analyzed separately to capture cardiac‐induced deformation of the liver. The liver is manually delineated and a novel image feature, namely, the histogram of the peak strain (HPS) value, is computed from the segmented liver region and is used to classify the liver as being either normal or fibrotic. Classification is achieved using a support vector machine algorithm. The in vivo study included 15 healthy volunteers (10 males; age range 30–45 years) and 22 patients (15 males; age range 25–50 years) with liver fibrosis verified and graded by transient elastography, and 10 patients only had a liver biopsy and were diagnosed with a score of F3‐F4. The proposed method demonstrates the usefulness and efficiency of extracting the HPS features from the sagittal slices for patients with moderate fibrosis. Cross‐validation of the method showed an accuracy of 83.7% (specificity = 86.6%, sensitivity = 81.8%).     

Low maternal serum concentrations of mannose‐binding lectin are associated with the risk of shorter duration of pregnancy and lower birthweight

Chronic inflammation has been implicated as the underlying mechanism responsible for the pathophysiology of preterm labour. Mannose‐binding lectin (MBL) plays a central role in the innate immune response and is thus an important component of the first line of defense. The aim of this study was to investigate whether serum concentrations of MBL correlated with the incidence of preterm birth and low birthweight in a cohort of women with signs of threatened preterm birth. A cohort of 60 patients who presented with regular contractions and/or short cervix (group A) between 24 and 32 weeks of gestation and 20 healthy controls (group B) who had no pregnancy complications and delivered at term were recruited into a prospective study. The following outcomes were recorded: presence of preterm labour and birthweight in all patients. MBL and high sensitivity C‐reactive protein levels were measured in all serum samples. The serum concentrations of MBL were significantly reduced in patients with threatened preterm labour (Group A), compared to the control Group B. Furthermore, infants born to Group A mothers with MBL deficiency (n = 13, MBL ≤100 ng/mL) had significantly lower birthweights, compared to those born to Group A women with normal MBL serum concentrations (P  < .0001). Our small cohort study demonstrated a strong association between MBL deficiency and preterm delivery, and associated low birthweight. MBL deficiency could thus be considered an important risk factor for preterm birth.     

Predicting factors of neurodevelopmental performance in children with phenylketonuria

In phenylketonuria (PKU), high phenylalanine (Phe) levels hamper neurodevelopment impairing executive function later in life. While the second has been more studied, fewer data exist on predictors of PKU patients' development in specific populations. To contribute to the field, we performed a retrospective analysis of predictors of neurodevelopment in PKU patients in a Portuguese cohort. We analyzed the retrospective data on the metabolic control of 89 patients, as their health and familial features. Griffith's Mental Development Scale performance at age 6 (GMDS6) was used to assess neurodevelopment. Our cohort included 14 GMDS6_low and 75 GMDS6_high patients. In a multivariate analysis, the better predictors of neurodevelopment were the metabolic control at age 3 and year of birth (n = 87, β₀ = −121, β₁ = −1.77, β₂ = 0.06, LRchi2(2) = 13.61, Prob > chi2 = 0.001, Pseudo R2 = 0.1773). With this model, it was possible to define a safety cut-off of 7.8 mg/dL for the Phe level at age 3 (sensitivity = 72.6%, specificity = 78.6%), confirming the safety of the cut-off of 6 mg/dL already used in the clinical practice. Our study supports the relevance of metabolic control to predict the neurodevelopment of PKU patients, in the historical context of the disease management.     

Propagation of electrical activity in uterine muscle during pregnancy: a review

The uterine muscle (the myometrium) plays its most evident role during pregnancy, when quiescence is required for adequate nourishment and development of the foetus, and during labour, when forceful contractions are needed to expel the foetus and the other products of conception. The myometrium is composed of smooth muscle cells. Contraction is initiated by the spontaneous generation of electrical activity at the cell level in the form of action potentials. The mechanisms underlying uterine quiescence during pregnancy and electrical activation during labour remain largely unknown; as a consequence, the clinical management of preterm contractions during pregnancy and inefficient uterine contractility during labour remains suboptimal. In an effort to improve clinical management of uterine contractions, research has focused on understanding the propagation properties of the electrical activity of the uterus. Different perspectives have been undertaken, from animal and in vitro experiments up to clinical studies and dedicated methods for non‐invasive parameter estimation. A comparison of the results is not straightforward due to the wide range of different approaches reported in the literature. However, previous studies unanimously reveal a unique complexity as compared to other organs in the pattern of uterine electrical activity propagation, which necessarily needs to be taken into consideration for future studies to be conclusive. The aim of this review is to structure current variegated knowledge on the properties of the uterus in terms of pacemaker position, pattern, direction and speed of the electrical activity during pregnancy and labour.     

Changes in muscle contractile characteristics and jump height following 24 days of unilateral lower limb suspension

We measured changes in maximal voluntary and electrically evoked torque and rate of torque development because of limb unloading. We investigated whether these changes during single joint isometric muscle contractions were related to changes in jump performance involving dynamic muscle contractions and several joints. Six healthy male subjects (21 ± 1 years) underwent 3 weeks of unilateral lower limb suspension (ULLS) of the right limb. Plantar flexor and knee extensor maximal voluntary contraction (MVC) torque and maximal rate of torque development (MRTD), voluntary activation, and maximal triplet torque (thigh; 3 pulses at 300 Hz) were measured next to squat jump height before and after ULLS. MVC of plantar flexors and knee extensors (MVCke) and triplet torque decreased by 12% (P = 0.012), 21% (P = 0.001) and 11% (P = 0.016), respectively. Voluntary activation did not change (P = 0.192). Absolute MRTD during voluntary contractions decreased for plantar flexors (by 17%, P = 0.027) but not for knee extensors (P = 0.154). Absolute triplet MRTD decreased by 17% (P = 0.048). The reduction in MRTD disappeared following normalization to MVC. Jump height with the previously unloaded leg decreased significantly by 28%. No significant relationships were found between any muscle variable and jump height (r < 0.48), but decreases in torque were (triplet, r = 0.83, P = 0.04) or tended to be (MVCke r = 0.71, P = 0.11) related to decreases in jump height. Thus, reductions in isometric muscle torque following 3 weeks of limb unloading were significantly related to decreases in the more complex jump task, although torque in itself (without intervention) was not related to jump performance.     

Similar increases in muscle size and strength in young men after training with maximal shortening or lengthening contractions when matched for total work

Training exclusively with eccentric (lengthening) contractions can result in greater muscular adaptations than training with concentric (shortening) contractions. We aimed to determine whether training-induced increases in muscle size and strength differed between muscles performing maximal lengthening (LC) or maximal shortening (SC) contractions when total external work is equivalent. Nine healthy young males completed a 9-week isokinetic (0.79 rad/s) resistance training program of the elbow flexors whereby they performed LC with one arm and an equivalent volume of total external work with the contralateral arm as SC. Training increased isometric peak torque for both LC (~10%) and SC (~20%) with no difference (P = 0.14) between conditions. There were also similar increases in isokinetic peak torque at both slow (0.79 rad/s) and fast (5.24 rad/s) shortening and lengthening peak torque for both LC (~8–10%) and SC (~9–20%). Training increased work per repetition similarly for both LC (~17%) and SC (~22%), in spite of ~40% greater work per repetition with LC. The increase in muscle cross-sectional area with training was also similar (P = 0.37) between LC (~6.5%) and SC (~4.6%). We conclude that increases in muscle size and strength with short-term unilateral resistance training are unrelated to muscle contraction type when matched for both exercise intensity (i.e. maximal contractions) and total external work.     

Use of rapid influenza diagnostic tests under field conditions as a screening tool during an outbreak of the 2009 novel influenza virus: Practical considerations

BackgroundRapid influenza diagnostic tests (RIDTs) are used in various settings as a first-line screen of patient specimens. During the initial outbreak of the 2009 novel influenza A/H1N1 virus, the Nebraska Public Health Laboratory (NPHL) adopted a testing algorithm, attempting to maximize the usefulness of RIDTs. However, it became apparent that a high percentage of the positive specimens received from off-site facilities were negative for influenza viruses by the confirmatory test, the Luminex xTAG Respiratory Viral Panel (RVP) molecular assay.ObjectivesTo explore the cause of discrepancies between RIDTs results obtained from on-site facility testing versus confirmatory testing performed at NPHL.Study designSpecimens (n = 336) tested with RIDTs at off-site facilities and screened for high-probability of containing H1N1 were sent to the NPHL for confirmatory testing by RVP.ResultsOf 336 specimens analyzed, 104 were negative for influenza A or B by both RIDT and RVP; 127 were positive by both tests; 102 were positive by RIDT only; and 3 were positive by RVP only. Using the RVP assay as the gold standard, overall RIDT characteristics in this screened population were: sensitivity = 97.7% (95%CI: 92.5, 99.3); specificity = 48.1% (95%CI: 40.4, 55.8); positive predictive value = 54.3% (95%CI: 47.0, 61.4); and negative predicative value = 97.1% (95%CI: 90.6, 99.1).ConclusionsThe results show that the confirmation of RIDT-positive results varied widely by testing site. Possible explanations for the discrepancies in performance characteristics include testing a narrowly defined sample population, test facility characteristics, facility work load, and seasonal timing.     

Effects of knee and ankle muscle fatigue on postural control in the unipedal stance

The aim of this study was to compare the effects of acute muscle fatigue of the ankle and knee musculature on postural control by immediate measures after performing fatiguing tasks (POST condition). One group of subjects (n = 8) performed a fatiguing task by voluntary contractions of the triceps surae (group TRI) and the other (n = 9) performed a fatiguing task by voluntary contractions of the quadriceps femoris (group QUA). Each muscle group was exercised until the loss of maximal voluntary contraction torque reached 50% (isokinetic dynamometer). Posture was assessed by measuring the centre of foot pressure (COP) with a force platform during a test of unipedal quiet standing posture with eyes closed. Initially (in PRE condition), the mean COP velocity was not significantly different between group TRI and group QUA. In POST condition, the mean COP velocity increased more in group QUA than in group TRI. The postural control was more impaired by knee muscle fatigue than by ankle muscle fatigue.