Comparison of short term variability indexes in cardiotocographic foetal monitoring

Concise indexes related to variability of foetal heart rate (FHR) are usually utilised for foetal monitoring; they enrich information provided by cardiotocography (CTG). Most attention is paid to the short term variability (STV), which relates to activity and reaction of autonomic nervous control of foetal heart. There is not a unique method to compute short term variability of the FHR but different formulas have been proposed and are employed in clinical and scientific environments: this leads to different evaluations and makes difficult comparative studies. Nine short term variability indexes: Arduini, Dalton, Organ, Sonicaid 8000, Van Geijn, Yeh, Zugaib a modified version of Arduini index and Standard Deviation were considered and compared to test their robustness in CTG applications. A large set of synthetic foetal heart rate series with known features were used to compare indexes performances. Different amounts of variability, mean foetal heart rate, storage rates, baseline variations were considered. The different indexes were in particular tested for their capability to recognise short term heart rate variability variation, their dependence on heart rate signal storage rate (as those provided by commercial cardiotocographic devices), on mean value of the foetal heart rate and on modifications of the floatingline, such in case of accelerations or decelerations.Concise statistical parameters relative to indexes scores were presented in comparative tables.Results indicate that although the indexes are able to recognise STV variation, they show substantial differences in magnitude and some in sensibility. Results depend on the frequency used to acquire and store FHR data (depending on devices); in general, the lower is data rate the more degraded are the results. Furthermore, results differently depend on FHR mean, some for their intrinsic definition; differences arise also in correspondences of accelerations and decelerations. Our results demonstrate that only indexes which refer directly to differences in FHR values, such as Organ and SD indexes, not show dependence on FHR mean.The use of the Standard Deviation index may provide efficient information while showing independence from the considered variables.Indexes performance in case of real cardiotocographic signals were also presented as examples.     

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.     

An algorithm for the recovery of fetal heart rate series from CTG data

Cardiotocography (simultaneous recording of fetal heart rate (FHR) and uterine contractions) is one of the most used diagnostic techniques to evaluate fetal well-being and to investigate the functional state of the fetal autonomic nervous system. Recently, great interest has been paid to the variability of the FHR, and its frequency analysis, as a base for a more objective analysis of the cardiotocographic (CTG) tracings. FHR signals are unevenly sampled series. To obtain evenly sampled series, cardiotocographs often use zero-order interpolation. Such process is simple and fast but results unsuitable for frequency analyses because it introduces alterations in the FHR power spectrum. An algorithm for the recovery of the true FHR series out of the zero-order interpolated CTG data was developed and evaluated.     

Computerised electronic foetal heart rate monitoring in labour: automated contraction identification

The foetal heart rate (FHR) response to uterine contractions is crucial to detect foetal distress by electronic FHR monitoring during labour. We are developing a new automated system (OxSys) for decision support in labour, using the Oxford database of intrapartum FHR records. We describe here a novel technique for automated detection of uterus contractions. In addition, we present a comparison of the new method with four other computerised approaches. During training, OxSys achieved sensitivity above 95% and positive predictive value (PPV) of up to 90% for traces of good quality. During testing, OxSys achieved sensitivity = 87% and PPV = 75%. For comparison, a second clinical expert obtained sensitivity = 93% and PPV = 80%, and all other computerised approaches achieved lower values. It was concluded that the proposed method can be employed with confidence in our study on foetal health assessment in labour and future OxSys development.     

Real-time analysis of foetal heart rate patterns using a computer system

The foetal heart rate and uterine contraction curves provide both continuous and real-time information on the foetus. In recent years, attempts have been made to automatically diagnose foetal distress using a computer to provide direct analysis of this information. In the present study, we performed pattern-analysis of the foetal heart rate and uterine contraction curves using a minicomputer on 476 mothers who gave birth at the hospital attached to Hamamatsu University School of Medicine from April 1978 to March 1980. We developed the algorithm for these curves. The algorithm was roughly divided into two groups, original signal process and pattern-recognition algorithms. Following the autocorrelation and noise reduction of original signals, the algorithm was analysed. The algorithmic analysis consisted of the calculation of baseline f.h.r. recognition of deceleration, recognition of uterine contraction, and classification of the deceleration pattern. By using these algorithms, the true diagnostic distribution rate was obtained: early deceleration: 76%, variable deceleration: 88%, late deceleration: 72%, and prolonged deceleration: 81%.     

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.     

The effect of change in sympatho-vagal balance on heart rate and blood pressure variability in the foetal lamb

Cardiac and vascular function is mainly under autonomic nervous control within seconds to minutes, although the control is not mature at birth. We studied sympatho-vagal control of heart rate and blood pressure in chronically catheterized foetal lambs in the last trimester of gestation. Power spectral analysis was used to quantitate the frequency-specific heart rate variability (HRV) and blood pressure variability. We performed 15 experiments in seven foetal lambs. These preliminary studies showed that parasympathetic blockade by atropine (eight experiments) had no significant effect on the distribution of HRV to different frequencies. Beta-sympathetic blockade by propranolol (seven experiments) decreased the ratio of low and mid to high frequency (0.025-0.13 to 0.13-1.00 Hz) HRV (P= 0.02). The increased high frequency HRV in the absence of a similar increase in blood pressure variability and tracheal pressure variability suggests enhanced baroreflex responsiveness after propranolol administration. The frequency-specific sympathetic control of HRV in foetal lambs, the change in ratio of low and mid to high frequency HRV, might have clinical implications in estimating the level of foetal sympathetic activation in the follow-up of high-risk pregnancies.     

Assessment of autonomic function in the late term fetus: The effects of sex and state

Researchers have reported associations between fetal sex and heart rate (FHR) and heart rate variability (FHRV) but rarely in the context of fetal behavioral sleep state. We examined differences in measures of fetal autonomic function by sex and sleep state. Fetal abdominal ECG monitoring technology was used to measure FHR and two measures of FHRV—standard deviation of FHR (SD) and beat-to-beat variability (RMSSD). FHR and movement patterns were also recorded with standard Doppler ultrasound monitor technology employed to code sleep states. Data were collected from 82 healthy fetuses ranging from 36 to 39 weeks gestation. A one-way MANOVA showed that FHR was significantly lower and SD was significantly higher for males than females. Independent samples t tests found that these sex differences were only in the active sleep state. There were no significant differences in RMSSD by sex. Repeated measures MANOVA for a subset that exhibited more than one state (N = 22) showed that SD was significantly different by state. RMSSD showed a marginally significant sleep state difference. In conclusion, fetal sex differences in HR and HRV may indicate more mature autonomic functioning in near-term males than females and fetal sleep state can influence abdominal fECG derived measures of FHR and FHRV.     

Porphyromonas gingivalis and adverse pregnancy outcomes: a review on its intricate pathogenic mechanisms

Abstract

Porphyromonas gingivalis (P. gingivalis), a Gram-negative facultative anaerobe of the oral cavity, is associated with the onset of various adverse pregnancy outcomes. P. gingivalis is linked with the development of preeclampsia, preterm labour, spontaneous abortion, gestational diabetes, foetal growth restriction, and misconception. The unique virulence factors, surface adhesions, enzymes of P. gingivalis can directly injure and alter the morphology, microbiome the foetal and maternal tissues. P. gingivalis can even exaggerate the production of cytokines, free radicals and acute-phase proteins in the uterine compartment that increases the risk of myometrial contraction and onset of preterm labour. Although evidence confirms the presence of P. gingivalis in the amniotic fluid and placenta of women with poor pregnancy outcomes, the intricate molecular mechanisms by which P. gingivalis initiates various antenatal and postnatal maternal and foetal complications are not well explained in the literature. Therefore, the present review aims to comprehensively summarise and highlight the recent and unique molecular pathogenic mechanisms of P. gingivalis associated with adverse pregnancy outcomes.     

Electronic model as an aid in teaching fetal heart rate monitoring

A model of the uterus-placenta-fetus system was designed using an electronic device which proportions at its outputs the representative signals of the fetal heart rate (FHR) and uterine contractions (UC). The uterus subsystem provides a voltage variable in time similar to the pressure of the UC. The placenta subsystem is controlled by the difference between the UC and the maternal arterial pressure as well as by the time in which the blood flow to the fetus is reduced. The fetus subsystem provides a voltage representative of the FHR.     

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.     

Fetal responses to induced maternal relaxation during pregnancy

Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-min guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal motor activity (FM), and increased FM-FHR coupling. Attribution of the two fetal cardiac responses to the guided imagery procedure itself, as opposed to simple rest or recumbency, is tempered by the observed pattern of response. Evaluation of correspondence between changes within individual maternal-fetal pairs revealed significant associations between maternal autonomic measures and fetal cardiac patterns, lower umbilical and uterine artery resistance and increased FHR variability, and declining salivary cortisol and FM activity. Potential mechanisms that may mediate the observed results are discussed.     

Antepartum cardiotocography: a study of fetal reactivity in frequency domain

Cardiotocography (CTG) is the most widely used diagnostic technique in clinical practice to monitor fetal health. Cardiotocographic recording also permits to assess maturation of the fetal autonomous nervous system (ANS): fetal heart rate (FHR) modifications may reveal ANS’ reactions to stimuli. To assess fetal reactivity, physicians evaluate specific clinical CTG parameters, generally, by means of visual inspection, thus depending on observer's expertise, with lack of reproducibility. Still nowadays, there is a very high intra- and inter-observer variation in the assessment of FHR patterns. More objective methods for CTG interpretation are of crucial importance. For adults, frequency analysis of heart rate variability (HRV) is a non-invasive and powerful method to investigate ANS activity. This frequency analysis can also be a valid support for a better knowledge of fetal ANS functional state and reactions. Indeed, fetal HRV is a good indicator of fetal well-being in non-stress conditions. Fetal reactivity is a very important CTG characteristic used to diagnose fetal distress, but its interpretation is still uncertain. The aim of this study is to characterise fetal reactivity proposing new fetal HRV frequency parameters to support a more exhaustive CTG analysis.     

A novel online method to monitor autonomic nervous activity based on arterial wall impedance and heart rate variability

This paper proposes a new method of evaluating autonomic nervous activity using the mechanical impedance of arterial walls and heart rate variability. The cardiovascular system is indispensable to life maintenance functions, and homeostasis is maintained by the autonomic nervous system. Accordingly, it is very important to be able to make diagnosis based on autonomic nervous activity within the body’s circulation. The proposed method was evaluated in surgical operations; the mechanical impedance of the arterial wall was estimated from arterial blood pressure and a photoplethysmogram, and heart rate variability was estimated using electrocardiogram R–R interval spectral analysis. In this paper, we monitored autonomic nervous system activity using the proposed system during endoscopic transthoracic sympathetic block surgery in eight patients with hyperhidrosis. The experimental results indicated that the proposed system can be used to estimate autonomic nervous activity in response to events during operations.     

Linear and nonlinear fetal heart rate analysis of normal and acidemic fetuses in the minutes preceding delivery

Linear and nonlinear fetal heart rate (FHR) indices, namely mean FHR, interval index (II), very low, low and high frequencies, approximate (ApEn) and sample entropy (SampEn), were computed, immediately before delivery, in the initial and final FHR tracing segments, from 48 normal, 10 mildly acidemic and 10 moderate-to-severely acidemic fetuses. Progression of labor was associated with a significant increase in linear frequency domain indices whereas nonlinear indices were significantly decreased. Moderate-to-severe fetal acidemia was associated with a significant decrease in nonlinear indices. The best discrimination between moderate-to-severe acidemic fetuses and the remaining cases was obtained combining II and ApEn(2,0.15), with a specificity of 71% and a sensitivity of 80%. These findings support the hypothesis of increased autonomic nervous system activity in the final minutes of labor and of decreased central nervous system activity, both in the final minutes of labor and in moderate-to-severe acidemic fetuses.     

Foetal and placental 11β‐HSD2: a hub for developmental programming

Foetal growth restriction (FGR), reflective of an adverse intrauterine environment, confers a significantly increased risk of perinatal mortality and morbidity. In addition, low birthweight associates with adult diseases including hypertension, metabolic dysfunction and behavioural disorders. A key mechanism underlying FGR is exposure of the foetus to glucocorticoids which, while critical for foetal development, in excess can reduce foetal growth and permanently alter organ structure and function, predisposing to disease in later life. Foetal glucocorticoid exposure is regulated, at least in part, by the enzyme 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2), which catalyses the intracellular inactivation of glucocorticoids. This enzyme is highly expressed within the placenta at the maternal–foetal interface, limiting the passage of glucocorticoids to the foetus. Expression of 11β‐HSD2 is also high in foetal tissues, particularly within the developing central nervous system. Down‐regulation or genetic deficiency of placental 11β‐HSD2 is associated with significant reductions in foetal growth and birth weight, and programmed outcomes in adulthood. To unravel the direct significance of 11β‐HSD2 for developmental programming, placental function, neurodevelopment and adult behaviour have been extensively investigated in a mouse knockout of 11β‐HSD2. This review highlights the evidence obtained from this mouse model for a critical role of feto‐placental 11β‐HSD2 in determining the adverse programming outcomes.     

Association of breathing movements to the variability of heart rate and blood pressure in foetal lambs

Heart rate (HR) variability and arterial blood pressure (BP) variability were analysed as functions of foetal breathing movements (FBMs) by means of power spectral analysis in seven foetal lambs during the third trimester of gestation. No evidence of FBM-related changes, either in mean HR, mean systolic or diastolic arterial pressures, were found. Mean arterial pulse pressure, HR variability, and BP variability increased during FBMs. The increase in BP variability occurred at frequencies higher than 0.35 Hz, i.e. those of FBMs. The increase in HR variability occurred at 0.07-1.0 Hz, i.e. at every frequency band except the lowest one. Thus, the increase in HR variability was not frequency-specifically related to FBMs. During FBMs the periodic variability of HR at frequencies > 0.35 Hz was only 10% of total HR variability. We suggest that the FBM-related changes of BP variability may be mediated by direct peripheral, hydraulic mechanisms. HR changes involve autonomic control systems: the vagal component of baroreflex seems to be relatively insensitive, whereas the very slow vasomotor component of HR variability is dominant.     

Some aspects of foetal and uteroplacental metabolism in cows with indwelling umbilical and uterine vascular catheters.

1. The experiments were carried out on conscious pregnant Jersey cows with intravascular catheters implanted during late gestation in umbilical and uterine vessels. All but three of fifteen animals delivered live healthy calves. 2. Rountine daily analyses were made of blood gas tensions, pH and packed cell volume in foetal and maternal blood; plasma concentrations of glucose, fructose, lactate and urea were also determined. Measurements of plasma free fatty acids and blood acetate concentrations were made less frequently. Foetal heart rate and arterial blood pressure were recorded in animals with an umbilical arterial catheter. 3. The concentration differences between foetal and maternal blood or plasma in glucose, urea and acetate were measured in fifteen animals. The maternal-to-foetal glucose and acetate gradients across the placenta were high while the foetal-to-maternal plasma urea differences were small. 4. In those animals with patent arterial and venous catheters, uterine and umbilical blood flows were measured together with the arteriovenous differences in 02, glucose, acetate and lactate so that rates of foetal and uterine consumption could be estimated. The rates of utilization of O2, glucose and acetate by the foetus were lower than the values for the whole uterus, while the uteroplacental metabolism of these substrates was very high. 5. Significant amounts of lactate, which appeared to be produced by the uteroplacental tissue, were utilized by the foetus; the remainder passed into the uterine venous blood. 6. The total substrate/O2 quotient for the foetus, calculated from the utilization of known metabolites, appeared to be greater than 1. Thus, in the calf some carbon accumulation from sources other than amino acids, the uptake of which was not measured, would seem to occur. These results and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep.     

Pathological and immunological findings in placentas from pregnant BALB/c mice infected with <Emphasis Type="Italic">Neospora caninum</Emphasis> at early and late stages of gestation

Neospora caninum is transmitted from a cow to its foetus by vertical transmission and the timing of infection in gestation is an important factor in determining the disease outcome. Few studies have explored the role of the placenta in the outcome of N. caninum infection during pregnancy. Here, we described the N. caninum presence, parasite load, local immune response, and histopathological lesions at the materno-foetal interface after infection of BALB/c mice at early and late stages of gestation. In mice infected at early gestation, N. caninum DNA was detected in foetoplacentary units 7 days post-infection (PI) and in the placenta, but not in viable foetuses on day 14 PI, indicating that the parasite was multiplying primarily in the placental tissues without reaching the foetus. Moreover, parasite DNA was detected in resorptions, suggesting that foetal death could be a consequence of infection. An increase in IFN-γ, TNF-α and IL-10 expression was observed in N. caninum PCR-positive placentas, which could favour N. caninum foetal transmission and be harmful to both the placenta and the foetus. Histopathological analysis revealed necrosis affecting both the maternal and foetal sides of the placenta. At late gestation, transmission occurred rapidly following infection (day 3 PI), but parasite were rarely found. In addition, an increase in cytokine expression was observed in spleen and placental tissues from infected animals, while a downregulation in IL-4 expression was only observed in the spleen. Finally, necrosis in the placenta was limited to the maternal side, suggesting that the parasite is mainly multiplying in the placental tissue at this stage. Thus, the results of the present study indicate that the placenta may be actively involved in N. caninum pathogenesis.     

Spectral analysis of heart rate fluctuations and optimum thermal management for low birth weight infants

Spectral analysis of heart rate variability is studied in 10 healthy growing premature infants to investigate the changes in autonomic balance achieved as a function of changes in skin temperature. Heart rate is obtained from ECG recordings and the power spectrum of beat-to-beat heart rate fluctuations is computed. The infants maintain mean rectal temperature within 36.3–37.2°C, while skin temperature changes. The respiratory rate does not change at the different servocontrol set points. Heart rate is found to increase slightly, but consistently. The low-frequency band (0.02–0.2 Hz), reflecting the interplay of the sympathetic and parasympathetic tone and known to be maximum at the thermoneutral zone, is maximum at 35.5 and 36°C and decreases gradually to a lower level at a servocontrol temperature of 36.5–37°C. The high-frequency band (0.2–2.0 Hz), coinciding with the respiratory peak and reflecting parasympathetic activity, is significantly elevated at 36°C (p<0.01). The minimum low: high ratio, indicating the minimum sympathetic-parasympathetic balance and possibly reflecting the most comfortable conditions, occurs at 36°C, although the differences are not statistically significant. Servocontrol skin temperature may thus be adapted, and possibly selected at 36°C for growing premature infants in an attempt to achieve thermal comfort and more balanced autonomic activity.