The psychophysiology of the maternal-fetal relationship

The enigmatic quality of the maternal-fetal relationship has been extolled throughout history with little empirical support. We apply time series analysis to data for 137 maternal-fetal pairs collected at 20, 24, 28, 32, 36, and 38 weeks gestation. Maternal heart rate and skin conductance data were digitized in tandem with fetal heart rate and motor activity. No temporal relations between fetal heart rate and either maternal variable were found, although averaged maternal and fetal heart rates were correlated from 32 weeks. Consistent temporal associations between fetal movement and maternal heart rate and skin conductance were detected. Fetal movement stimulated rises in each parameter, peaking at 2 and 3 s, respectively. Associations did not change over gestation, were unaffected by a maternal stressor, and showed within-pair stability. The bidirectional nature of the maternal-fetal relationship is considered.     

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.     

母血HIF-1α水平联合胎心监护预测胎儿窘迫的价值

目的探讨母血中缺氧诱导因子-1α（HIF-1α）水平及联合胎心监护预测胎儿窘迫的价值。方法选取40名正常妊娠孕妇（正常妊娠组）及95例胎儿窘迫孕妇（胎儿窘迫组）测定血清HIF-1α水平,同时进行胎心监护分析及新生儿Apgar评分。结果胎儿窘迫组母血HIF-1α水平为105.73±31.12pg/L,明显高于正常妊娠组（41.48±18.91pg/L）;其中,胎儿窘迫组胎心监护阳性者,母血HIF-1α水平为138.98±30.56 pg/L;可疑者为94.21±28.93 pg/L,两者的HIF-1α水平均明显高于正常妊娠组,差异有统计学意义（P〈0.01）;而胎心监护为阴性者母血HIF-1α水平为47.34±18.76pg/L,与正常妊娠组比较,差异无统计学意义（P〉0.05）;在胎儿窘迫三组间,HIF-1α两两比较,差异有统计学意义（P〈0.05）。胎儿窘迫组母血HIF-1α水平与新生儿Apgar评分呈负相关。结论母血HIF-1α水平可作为预测胎儿窘迫的一种新指标,胎心监护联合HIF-1α水平测定可提高判断胎儿宫内缺氧的准确性。     

Antenatal origins of individual differences in heart rate

This study examines prenatal-to-postnatal stability in heart rate and variability from mid-gestation through the first year of life. Fetal heart rate data were collected from 52 healthy fetuses at 24, 30, and 36 weeks gestation, and again at 2 weeks and 12 months of age. Fetal heart rate measures were stable during gestation and positively associated with neonatal and infant measures. Maternal pulse rate and oxygen saturation were moderately associated with fetal heart rate. Together, fetal cardiac (heart rate and variability) and maternal physiologic measures (blood pressure and oxygen saturation) explained 40 and 48% of the variance in heart rate and variability, respectively, at 1 year of age. These common measures of individual differences in autonomic function are enduring characteristics that originate during fetal development.     

Ellipsoidal head model for fetal magnetoencephalography: forward and inverse solutions

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.     

The event synchronous canceller algorithm removes maternal ECG from abdominal signals without affecting the fetal ECG

Fetal monitoring using abdominally recorded signals (ADS) allows physicians to detect occurring changes in the well-being state of the fetus from the beginning of pregnancy. Mainly based on the fetal electrocardiogram (fECG), it provides the long-term fetal heart rate (fHR) and assessment of the fetal QRS morphology. But the fECG component in ADS is obscured by the maternal ECG (mECG), thus removal of the mECG from ADS improves fECG analysis. This study demonstrates the performance of the event-synchronous interference canceller (ESC) in mECG removal from ADS data, recorded during pregnancy and labor. Its advantage as a compensation method for extended ADS processing is 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 method for the automatic reconstruction of fetal cardiac signals from magnetocardiographic recordings

Fetal magnetocardiography (fMCG) allows monitoring the fetal heart function through algorithms able to retrieve the fetal cardiac signal, but no standardized automatic model has become available so far. In this paper, we describe an automatic method that restores the fetal cardiac trace from fMCG recordings by means of a weighted summation of fetal components separated with independent component analysis (ICA) and identified through dedicated algorithms that analyse the frequency content and temporal structure of each source signal. Multichannel fMCG datasets of 66 healthy and 4 arrhythmic fetuses were used to validate the automatic method with respect to a classical procedure requiring the manual classification of fetal components by an expert investigator. ICA was run with input clusters of different dimensions to simulate various MCG systems. Detection rates, true negative and false positive component categorization, QRS amplitude, standard deviation and signal-to-noise ratio of reconstructed fetal signals, and real and per cent QRS differences between paired fetal traces retrieved automatically and manually were calculated to quantify the performances of the automatic method. Its robustness and reliability, particularly evident with the use of large input clusters, might increase the diagnostic role of fMCG during the prenatal period.     

The influence of coincidence of fetal and maternal QRS complexes on fetal heart rate reliability

Bioelectrical fetal heart activity being recorded from maternal abdominal surface contains more information than mechanical heart activity measurement based on the Doppler ultrasound signals. However, it requires extraction of fetal electrocardiogram from abdominal signals where the maternal electrocardiogram is dominant. The simplest technique for maternal component suppression is a blanking procedure, which relies upon the replacement of maternal QRS complexes by isoline values. Although, in case of coincidence of fetal and maternal QRS complexes, it causes a loss of information on fetal heart activity. Its influence on determination of fetal heart rate and the variability analysis depends on the sensitivity of the heart-beat detector used. The sensitivity is defined as an ability to detect the incomplete fetal QRS complex. The aim of this work was to evaluate the influence of the maternal electrocardiogram suppression method used on the reliability of FHR signal being calculated.     

Fetal cyclic motor activity in diabetic pregnancies: sensitivity to maternal blood glucose

Spontaneous fetal movement in the last third of human gestation is dominated by irregular oscillations on a scale of minutes (cyclic motility, CM). The core properties of these oscillations are stable during the third trimester of gestation in normal fetuses, but disrupted by poorly controlled maternal diabetes. Here we investigated whether fetal CM is linked to short-term instabilities in maternal glucose metabolism. The fetuses of 40 mothers with type I (n = 28) or gestational (n = 12) diabetes were studied one to six times between 27 and 40 postmenstrual weeks of gestation. Fetal movement and maternal blood glucose concentration were measured during two separate periods of fetal activity in each session. Fetal CM was quantified with spectral analysis. Early in the third trimester, changes in the rate of oscillation in fetal CM between the two periods of activity were inversely related to changes in maternal blood glucose levels. Fetal CM was unrelated to concurrent maternal blood glucose levels at any point in the third trimester. The pattern of results suggests that disruption of the temporal organization of spontaneous fetal motor activity in pregnancies complicated by maternal diabetes represents an acute response to fluctuations in the metabolic environment rather than an alteration of CM development.     

Fetal surgery for congenital heart disease.

Certain congenital heart defects, which present at birth as complex morphologic defects, are actually the result of a relatively simple primary lesion and the subsequent acquired development of a complex secondary lesion during gestation. Moreover, fetal heart approach during gestation can prevent simple cardiac lesions from such development. Specific structural lesions can be diagnosed before 12 weeks of gestation by transvaginal fetal echocardiography, and animal experiments have shown that direct or indirect fetal cardiac approach and fetal cardiac bypass are technically feasible. A number of fetal bypass models have resulted in long-term survivors, with for example, the delivery of normal lambs at full-term gestation. Also, successful full-term delivery has been obtained after fetal cardiac intervention. The success of fetal cardiac bypass was accomplished by the use of total spinal anesthesia and the administration of indomethacin. Moreover, a 42 % long-term survival after fetal cardiopulmonary bypass in a fetal lamb model has been reported. Maternal risk related to fetal bypass should be considered carefully alongside fetal risks and benefits. Most fetal malformations do not directly threaten maternal health, yet the procedures required to address fetal malformations can produce significant maternal risk and discomfort and subsequent pregnancies may be jeopardized. Further investigation of maternal outcome is required. Deep exploration of fetal and maternal pathophysiologic responses to intervention and comprehensive investigation is required to overcome current limitations, and should precede clinical trials as many problems remain to be solved before these techniques can be applied to human beings.     

基于非负盲分离的胎儿心率检测方法

胎儿心率监测是一种有效评估胎儿当前健康状况的重要参考依据。为了可以快速准确地获取胎儿心率,该文提出一种基于非负盲分离的胎儿心率检测方法。该方法首先对采集得到的腹壁信号进行预处理,平稳小波变换后重构出母亲心电信号;接着,采用相减法去除母亲心电信号,再把剩下含有噪声的胎儿心电信号通过时频变换得到Born-Jordan分布;最后,利用非负矩阵分解得到胎儿心电的特征信号,检测其R波位置求得胎儿瞬时心率。实验结果表明,该方法可以快速、准确有效地获得胎儿地瞬时心率数据。     

超声测量胎儿颈项透明层厚度在产前筛查中的应用

产前筛查是目前诊断胎儿畸形的必要手段,胎儿颈项透明层（nuchal translucency,NT）增厚与胎儿染色体异常、先天性心脏病、自然流产等不良临床结局密切相关,孕11-13＋6w超声测量胎儿颈项透明层（NT）厚度是孕早期诊断胎儿畸形最有意义的一项检查,特别是筛查染色体异常的较敏感的指标。为了明确超声测定胎儿颈项透明层厚度在产前诊断中的意义,现就国内外文献对胎儿颈项透明层与产前超声的关系进行综述。     

Trans-abdominal monitoring of fetal arterial blood oxygenation using pulse oximetry

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.     

Fetal magnetocardiography

The electrical activities of the heart causes weak changes of the magnetic field, which can be recorded as magnetocardiogram (MCG). Fetal cardiac magnetic activity is measured in the order of less than 10 pT. An advance of the novel technology of a superconducting quantum interference device enabled the first recording of fetal MCG (FMCG) in 1974. In Japan, FMCG instrument (MC6400, Hitachi High-Technologies Ltd) was approved as a diagnostic tool by Japanese Government in 2003 owing to the cooperative studies of Tsukuba University, National Cardiovascular Center and Hitachi Ltd. FMCG offers similar information to a fetal electrocardiogram, which is difficult to be recorded because the fetal skin is covered with fatty caseous vernix of weak electrical conductivity in the second and third trimester of pregnancy. Magnetic flux can pass through the fat layer, and thus FMCG can measure the electrical activity of the fetal heart. Besides FMCG has far higher resolutions in time domain than echocardiography does. The amplitude of FMCG signals depends on the size of fetal heart and the distance between the sensors and the fetal heart. The amplitudes of the QRS, P and T waves increases with gestational age. Since the amplitudes of P and T waves are often weak, averaging of FMCG signals is needed to improve the signal-to-noise ratio. Current-arrow map is a useful mapping technique even in FMCG. FMCG has been applied in the prenatal diagnosis of fetal arrhythmias such as bradyarrhythmia (atrioventricular block, long QT syndrome, etc), tachyarrhythmia (supraventricular tachycardia, atrial flutter, atrial fibrillation and WPW syndrome, etc) and extrasystoles. Fetal cardiomegaly with myocardial abnormalities can be also diagnosed by FMCG. Applications of FMCG for fetal heart rate monitoring using beat-to-beat variability have been also studied to obtain better information on fetal well-beings.     

Prenatal development of intrafetal and maternal-fetal synchrony

Fetal and maternal data were monitored serially at 6 gestational ages from 20 to 38 weeks in 195 Peruvian fetuses. Digitized data included fetal heart rate and motor activity, as well as maternal heart rate and electrodermal conductance. Time series analysis evaluated the development of synchrony in 2 streams of fetal functioning and between mothers and fetuses. Intrafetal synchrony between heart rate and motor activity developed in an orderly fashion, with peak cross-correlation approaching an asymptote at 5 s at 28 weeks. Synchrony was not observed between fetal heart rate and maternal measures. Fetal motor activity exhibited synchrony with both maternal electrodermal and heart rate activity. Implications for revealing fundamental properties of neural development prior to birth are discussed. ((c) 2006 APA, all rights reserved).     

Unopposed orexic pathways in the developing fetus

Fetal swallowing has important roles in fetal gastrointestinal development, and perhaps fetal somatic growth and maturation. Ingestive behavioral responses must develop in utero to provide for acquisition of water and food intake during the neonatal period. At birth, the rat, ovine and human fetus have developed mechanisms to acquire food via intact mechanisms of taste, suckling and swallowing. Our preliminary studies suggest that in sheep and likely in human fetuses, putative orexic-mediated ingestive responses are present near term gestation. We hypothesize that both orexic (appetite) and satiety mechanisms develop during the last third of gestation and the related neurotransmitters involved in this process are functional. The potential in utero imprinting of orexic mechanisms may influence infant, childhood and ultimately adult appetite "set-points". Thus, dysfunctional appetite, and perhaps obesity, may result from maternal environmental influences during critical stages of development.     

No effect of nutrient restriction from gestational days 28 to 78 on immunocytochemically detectable growth hormone-releasing hormone (GHRH) neurons and GHRH receptor colocalization in somatotropes of the ovine female fetus

The maternal environment affects fetal development and may permanently affect the physiology of the adult. Fetal growth hormone (GH) secretion is increased by maternal undernutrition but the physiological mechanisms responsible for this increase are unknown. We have recently found evidence suggesting that the GHRH component of the fetal neuroendocrine GH axis may be perturbed by undernutrition. This study sought to determine the effect of maternal undernutrition on immunocytochemically detectable GHRH neurons and the expression of GHRH receptors by somatotropes in the pituitary gland. Ewes were grouped (n=12 per group) randomly into control (fed 100% of requirements) or nutrient restricted (fed 50% of requirements) from days 28 to 78 of gestation, corresponding to the period from implantation to the end of placentation. At day 78, half the ewes were killed and the fetal brains were perfused. The remaining ewes were re-alimented to 100% of nutritional requirements and killed at day 135. There was no effect of nutrition restriction or age on the number of GHRH neurons. Similarly, the mean density and percentage of somatotropes expressing GHRH receptors was not significantly different between treatment groups at either age. This study found no effect, as determined by immunocytochemistry, of nutrient restriction on the GHRH component of the fetal neuroendocrine GH axis. It remains to be established if the release of GHRH and responsiveness of somatotropes to GHRH in the fetus are affected by undernutrition.     

Entropy-based automated classification of independent components separated from fMCG

Fetal magnetocardiography (fMCG) is a noninvasive technique suitable for the prenatal diagnosis of the fetal heart function. Reliable fetal cardiac signals can be reconstructed from multi-channel fMCG recordings by means of independent component analysis (ICA). However, the identification of the separated components is usually accomplished by visual inspection. This paper discusses a novel automated system based on entropy estimators, namely approximate entropy (ApEn) and sample entropy (SampEn), for the classification of independent components (ICs). The system was validated on 40 fMCG datasets of normal fetuses with the gestational age ranging from 22 to 37 weeks. Both ApEn and SampEn were able to measure the stability and predictability of the physiological signals separated with ICA, and the entropy values of the three categories were significantly different at p <0.01. The system performances were compared with those of a method based on the analysis of the time and frequency content of the components. The outcomes of this study showed a superior performance of the entropy-based system, in particular for early gestation, with an overall ICs detection rate of 98.75% and 97.92% for ApEn and SampEn respectively, as against a value of 94.50% obtained with the time-frequency-based system.     

在孕9周前检测孕妇外周血中胎儿的性别

目的：评价使用孕妇外周血中的胎儿细胞和游离DNA进行无创伤性产前诊断的可能性。方法：研究对象为150名孕5－9周的孕妇。使用淋巴细胞分离液和3％的明胶分离胎儿细胞。使用荧光定量PCR（FISH）检测母血中胎儿细胞Y染色体的末端。同时使用巢氏PCR和荧光定量PCR（FQ-PCR)检测150名孕妇血浆中的胎儿SRY基因。结果：FISH,巢氏PCR以及FQ-PCR三种方法的敏感性分别为73.2％，78％和85.4％，特异性分别为96.2％，100％和100％。使用FISH，最早在孕49天检测到胎儿细胞，使用巢氏PCR和FQ-PCR最早在孕49天和42天检测到孕妇血浆中的胎儿游离DNA.结论：三种方法对无创伤性产前诊断都是适合的。但其中FQ-PCR因其检测时间较早而成为最优选择。