Annette Wacker-Gussmann

Auditory habituation in the fetus and neonate: an fMEG study.

Habituation--the most basic form of learning--is used to evaluate central nervous system (CNS) maturation and to detect abnormalities in fetal brain development. In the current study, habituation, stimulus specificity and dishabituation of auditory evoked responses were measured in fetuses and newborns using fetal magnetoencephalography (fMEG). An auditory habituation paradigm consisting of 100 trains of five 500 Hz tones, one 750 Hz tone (dishabituator) and two more 500 Hz tones, respectively, were presented to 41 fetuses (gestational age 30-39 weeks) and 22 newborns or babies (age 6-89 days). A response decrement between the first and fifth tones (habituation), an increment between the fifth tone and the dishabituator (stimulus specificity) and an increment between the fifth (last tone before the dishabituator) and seventh tones (first tone after the dishabituator) (dishabituation) were expected. Fetuses showed weak responses to the first tone. However, a significant response decrement between the second and fifth tones (habituation) and a significant increment between the fifth tone and the dishabituator (stimulus specificity) were found. No significant difference was found for dishabituation nor was a developmental trend found at the group level. From the neonatal data, significant values for stimulus specificity were found. Sensory fatigue or adaptation was ruled out as a reason for the response decrement due to the strong reactions to the dishabituator. Taken together, the current study used fMEG to directly show fetal habituation and provides evidence of fetal learning in the last trimester of pregnancy.

Diagnosis and Treatment of Fetal Arrhythmia

AIMS 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 rhythm are 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. METHODS 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. RESULTS AND CONCLUSIONS This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques.

Reticulocyte haemoglobin content as a marker of iron deficiency

Objective To evaluate reticulocyte haemoglobin content (CHr), compared with ferritin, transferrin saturation (TS) and mean corpuscular volume (MCV), as a marker of iron deficiency (ID). Design Retrospective analysis of clinically indicated blood samples taken between February 2010 and October 2012. Setting Single-centre neonatal care unit. Patients 210 very preterm (gestational age <32 weeks) or very low birthweight infants (birth weight <1500 g) at 3–4 months corrected age. Main outcome measures Complete blood count, CHr, ferritin and TS determined as part of a standard follow-up examination. To detect the optimal CHr cut-off, ID was defined by the presence of more than two of the following three criteria: MCV <75 fL, TS <10%, ferritin <30 µg/L. Results 210 preterm infants were included at a corrected age of (median (IQR)) 3.5 (3.0–4.0) months and with a CHr of 29.7 (28.6–30.7) pg. There were correlations between CHr and MCV (r=0.54, p <0.0001) and between CHr and TS (r=0.44, p <0.0001). There were 27 (13.4%) iron-deficient infants, and two infants (1%) fulfilled criteria of ID-anaemia. CHr was lower in infants with ID (26.4 (23.8–28.7) pg) than in those without (29.9 (29.0–30.8) pg, p <0.0001). The optimal CHr cut-off for detecting ID was 29 pg (sensitivity 85%, specificity 73%). Areas under the receiver operating characteristic curve for detection of ID tended to be higher for CHr compared with ferritin (0.92 vs 0.75), TS (0.90 vs 0.82) and MCV (0.81 vs 0.72). Conclusions CHr seems to be a suitable marker for latent ID in preterm infants at 3–4 months corrected age and may be superior to ferritin, TS and MCV.

Fetal arrhythmias associated with cardiac rhabdomyomas

BACKGROUND Primary heart tumors in fetuses are rare and mainly represent rhabdomyomas. The tumors have a variable expression and can be associated with arrhythmias, including both wide and narrow QRS tachycardia. Although multiple Doppler techniques exist to assess fetal heart rhythm, it can be difficult to record precise electrophysiological abnormalities in fetal life. OBJECTIVE Investigations defining precise electrophysiological diagnosis were performed by using fetal magnetocardiography (fMCG). METHODS In addition to routine fetal echocardiography, fMCG was used to investigate electrophysiological rhythm patterns in a series of 10 fetuses with cardiac rhabdomyomas. RESULTS The mean gestational age of the fetuses was 28.6 ± 4.7 weeks. The multiple rhabdomyomas were mainly located in the right and left ventricles as well as around the atrioventricular groove. Arrhythmias or conduction abnormalities were diagnosed in all 10 patients, although only 6 of them were referred due to that indication. Remarkably, 80% (8 of 10) had associated Wolff-Parkinson-White pre-excitation. In addition, we found prominent P waves in 4 fetuses. CONCLUSION In fetuses with rhabdomyomas, a disease where rhythm pathology is common, precise electrophysiological diagnosis can now be made by fMCG. fMCG is complimentary to echocardiography for rhythm assessment and can detect conduction abnormalities that are not possible to diagnose prenatally with M-mode or pulsed Doppler ultrasound. Risk factor assessment using fMCG can support pregnancy management and postnatal treatment and follow-up.

Sensitivity to Auditory Spectral Width in the Fetus and Infant – An fMEG Study

Auditory change detection is crucial for the development of the auditory system and a prerequisite for language development. In neonates, stimuli with broad spectral width like white noise (WN) elicit the highest response compared to pure tone and combined tone stimuli. In the current study we addressed for the first time the question how fetuses react to “WN” stimulation. Twenty-five fetuses (Mage = 34.59 weeks GA, SD ± 2.35) and 28 healthy neonates and infants (Mage = 37.18 days, SD ± 15.52) were tested with the first paradigm, wherein 500 Hz tones, 750 Hz tones, and WN segments were randomly presented and auditory evoked responses (AERs) were measured using fetal magnetoencephalography (fMEG). In the second paradigm, 12 fetuses (Mage = 25.7 weeks GA, SD ± 2.4) and 6 healthy neonates (Mage = 23 days and SD ± 6.2) were presented with two auditory oddball conditions: condition 1 consisted of attenuated WN as standard and 500 Hz tones and WN as deviants. In condition 2, standard 500 Hz tones were intermixed with WN and attenuated WN. AERs to volume change and change in spectral width were evaluated. In both paradigms, significantly higher AER amplitudes to WN than to pure tones replicated prior findings in neonates and infants. In fetuses, no significant differences were found between the auditory evoked response amplitudes of WN segments and pure tones (both paradigms). A trend toward significance was reached when comparing the auditory evoked response amplitudes elicited by attenuated WN with those elicited by WN (loudness change, second paradigm). As expected, we observed high sensibility to spectral width in newborns and infants. However, in the group of fetuses, no sensibility to spectral width was observed. This negative finding may be caused by different attenuation levels of the maternal tissue for different frequency components.

Electrophysiologic features of fetal ventricular aneurysms and diverticula

Congenital ventricular wall defects are very rare and include congenital ventricular aneurysms (CVAs) and diverticula (CVDs).

Development and application of an automated extraction algorithm for fetal magnetocardiography – normal data and arrhythmia detection

Abstract Introduction: Current standard methods of monitoring fetal heart function are mainly based on echocardiography, which provides indirect information (through mechanical assessment) of the fetal heart rhythm. Fetal magnetocardiography (fMCG) allows a reliable quantification of the temporal structure of fetal heart signals. However, its application in clinical studies is difficult because extracting the fetal heart signal for most current applications requires user intervention. To overcome this limitation, we developed a completely automated extraction algorithm. Patients and methods: The fMCG recordings were acquired using a 156-channel biomagnetic system. To perform an automated analysis, a combination of orthogonal projection and independent component analysis was used. fMCG recordings from 69 healthy uncomplicated singleton pregnancies with normally developing fetuses were included in the study. Results: The normal values achieved by the automated algorithm were comparable to previously published data. The majority of the cardiac time intervals were positively correlated with gestational age (GA). The ST segment, T wave and QT interval did not show any correlation. Conclusions: The automated detection of fetal heart signals was possible beginning at a GA of 19 weeks. This automated analysis of fMCG recordings might be an objective and easily applicable approach for clinicians to analyze fetal heart signals.

Fetal Atrial Flutter: Electrophysiology and Associations With Rhythms Involving an Accessory Pathway

Background Atrial flutter (AFl) accounts for up to one third of all fetal tachyarrhythmias and can result in premature delivery, hydrops, and fetal death in 10% of cases; however, the electrophysiology of AFl in utero is virtually unstudied. Methods and Results In this observational study, we reviewed 19 fetal magnetocardiography studies from 16 fetuses: 15 fetuses (21–38 weeks’ gestation) referred with an echocardiographic diagnosis of AFl and 1 fetus (20 weeks’ gestation) referred with a diagnosis of tachycardia that was shown by fetal magnetocardiography to have transient AFl in addition to atrioventricular reciprocating tachycardia. Thirteen fetuses showed AFl during the fetal magnetocardiography session, including 4 that presented prior to the third trimester. Five fetuses had incessant AFl; all but 1 of the others with AFl showed additional significant rhythms. Specifically, AFl showed a strong association with rhythms involving an accessory pathway: atrioventricular reciprocating tachycardia, blocked reentrant premature atrial contractions, and ventricular preexcitation. The observed initiations and terminations of AFl most often involved reentrant premature atrial contractions. Spontaneous termination of AFl showed AFl cycle length oscillations. Nine fetuses with 2:1 AFl also showed periods of 4:1 conduction or variable conduction that oscillated between 2:1 and 4:1; however, 3:1 AFl was relatively rare. Conclusions Fetal AFl can occur as early as midgestation and is often accompanied by atrioventricular reciprocating tachycardia and other rhythms associated with an accessory pathway. The findings depict critical differences in the electrophysiology of AFl in the fetus versus the neonate.

Fetal cardiac time intervals in healthy pregnancies – an observational study by fetal ECG (Monica Healthcare System)

Abstract Background: Fetal electrocardiogram (fECG) can detect QRS signals in fetuses from as early as 17 weeks’ gestation; however, the technique is limited by the minute size of the fetal signal relative to noise ratio. The aim of this study was to evaluate precise fetal cardiac time intervals (fCTIs) with the help of a newly developed fetal ECG device (Monica Healthcare System). Methods: In a prospective manner we included 15–18 healthy fetuses per gestational week from 32 weeks onwards. The small and wearable Monica AN24 monitoring system uses standard ECG electrodes placed on the maternal abdomen to monitor fECG, maternal ECG and uterine electromyogram (EMG). Fetal CTIs were estimated on 1000 averaged fetal heart beats. Detection was deemed successful if there was a global signal loss of less than 30% and an analysis loss of the Monica AN24 signal separation analysis of less than 50%. Fetal CTIs were determined visually by three independent measurements. Results: A total of 149 fECGs were performed. After applying the requirements 117 fECGs remained for CTI analysis. While the onset and termination of P-wave and QRS-complex could be easily identified in most ECG patterns (97% for P-wave, PQ and PR interval and 100% for QRS-complex), the T-wave was detectable in only 41% of the datasets. The CTI results were comparable to other available methods such as fetal magnetocardiography (fMCG). Conclusions: Although limited and preclinical in its use, fECG (Monica Healthcare System) could be an additional useful tool to detect precise fCTIs from 32 weeks’ gestational age onwards.

Fetal suppression burst pattern in Ohtahara syndrome visualized by fetal magnetoencephalography

Maternal age, y 30.8±4.7 32.4±5.3 26.9±4.8 27.0±1.4 26.81±4.7 27.83±6.6 28.93±6.01 25.4±2.7 Parity Primigravida 19 (28.4) 6 (75.0) 16 (69.6) 1 (50.0) 24 (46.2) 6 (50.0) 11 (35.5) 2 (40.0) Multigravida 48 (71.6) 2 (25.0) 7 (30.4) 1 (50.0) 28 (53.8) 6 (50.0) 20 (64.5) 3 (60.0) Gestational age, wk 39.41±1.3 39.5±1.2 39.22±1.1 38.5±0.7 39.25±1.2 38.58±1.3 38.90±0.9 38.80±1.3 Infant birth weight, g 3428.4±420.9 3444.9±369.5 3480.4±347.5 2915.0±5.4 NA NA NA NA