Fetal behavioral states are stable over daytime - evidence by longitudinal and cross-sectional fetal biomagnetic recordings.

AIMS: Fetal behavioral states can be distinguished by biomagnetic recordings. We performed a longitudinal and a cross-sectional study to address the question whether the distribution of fetal behavioral states changes during the daytime. METHODS: For the longitudinal study, 32 magnetocardiographic recordings were performed on a singleton pregnancy on a weekly basis. On each examination day, two recordings were performed at different times between 25 and 40 weeks of gestation. For the cross-sectional study, fetal magnetocardiograms (fMCG) were recorded in a group of 32 singleton pregnancies matched for gestational age and daytime to the longitudinal study. The recordings were separated into two gestational age groups (less and more than 32 weeks). Fetal behavioral states were extracted from actocardiograms generated from MCG. RESULTS: No significant differences in fetal behavioral state distribution were found between morning and afternoon recordings in either the longitudinal or the cross-sectional study. CONCLUSION: This is the first magnetographic approach to show that daytime does not influence the distribution of fetal behavioral states in standardized recordings of 30 min length. This result implies that fetal magnetography recordings at normal daytimes can be combined without a bias and future recordings can be conducted independently of daytime as long as the varying behavioral states are generally taken into account during analysis.

Is there a relationship between fetal brain function and the fetal behavioral state? A fetal MEG-study.

AIM: Fetal magnetography enables the recording of biomagnetic fetal signals, including fetal heart and fetal brain signals. These signals allow the determination of fetal behavioral states and functional brain signals with auditory evoked responses (AER). In the current study, we investigated how the behavioral state influences the AER and how stimulation affects fetal state. METHODS: One hundred and four fetuses in three age groups (28-31 weeks, 32-35 weeks and 36-41 weeks) were recorded with and without auditory stimulation. Both sessions were scored for fetal states. The AER latency was determined for each state separately. Forty-five additional subjects were recorded with two sessions of 10 min without stimulation to investigate a possible time effect on state changes. RESULTS: The state distribution was significantly different between stimulation and no stimulation conditions. The AER latencies were significantly shorter in active sleep (P=0.013) and active wakefulness (P=0.004) compared to quiet sleep. CONCLUSION: Auditory stimulation has an effect on fetal states. The state information should be taken into account for the analysis of AER latencies.

Family History of Diabetes Is Associated With Delayed Fetal Postprandial Brain Activity.

Introduction: We have previously shown that fetuses of mothers with gestational diabetes mellitus (GDM) and insulin resistance exhibit a prolongation of fetal auditory event-related brain responses (fAER) compared to fetuses of normal glucose tolerant women during an oral glucose tolerance test (oGTT). This implies that maternal metabolism may program the developing fetal brain. We now asked whether a family history of type 2 diabetes without metabolic programing also impacts fetal brain activity. We therefore investigated brain activity in fetuses of normal glucose tolerant mothers with and without family history of type 2 diabetes (FHD+ and FHD-). Methods: A 75 g oGTT was performed in healthy pregnant women. Plasma glucose and insulin levels were measured after 0, 60, and 120 min. Each blood draw was preceded by fetal magnetoencephalographic (fMEG) recordings of fAER. From a group of 167 participants, a subsample of 52 metabolically healthy women, 37 with a negative, and 15 with a positive FHD (at least one first- or second-degree relative) was carefully selected based on the following inclusion criteria: inconspicuous pregnancy, no GDM, BMI 18.5-30 kg/m2, no preterm birth and at least two fMEG with detectable fetal responses during oGTT. Results: An ANOVA showed a significant interaction between fMEG measurement time during the oGTT and FHD on fAER latency [F (2) = 4.163, p = 0.018]. Fetuses of mothers with FHD+ had a prolonged fAER (273 ± 113 ms) compared to fetuses of mothers with FHD- (219 ± 69 ms) at 60 min during the oGTT [F (1) = 4.902, p = 0.032]. There were no significant differences in age, BMI before pregnancy, weight gain during pregnancy and gestational age between the groups. Maternal glucose levels and insulin sensitivity were also not significantly different. Discussion: In addition to the previously shown influence of maternal metabolism on fetal brain activity, maternal family history of diabetes (FHD) is also linked to fetal postprandial brain activity. This indicates that genetic and/or epigenetic factors modulate the postprandial brain response of the developing fetus.

Heart rate variability parameters and fetal movement complement fetal behavioral states detection via magnetography to monitor neurovegetative development.

Fetal behavioral states are defined by fetal movement and heart rate variability (HRV). At 32 weeks of gestational age (GA) the distinction of four fetal behavioral states represented by combinations of quiet or active sleep or awakeness is possible. Prior to 32 weeks, only periods of fetal activity and quiesence can be distinguished. The increasing synchronization of fetal movement and HRV reflects the development of the autonomic nervous system (ANS) control. Fetal magnetocardiography (fMCG) detects fetal heart activity at high temporal resolution, enabling the calculation of HRV parameters. This study combined the criteria of fetal movement with the HRV analysis to complete the criteria for fetal state detection. HRV parameters were calculated including the standard deviation of the normal-to-normal R-R interval (SDNN), the mean square of successive differences of the R-R intervals (RMSSD, SDNN/RMSSD ratio, and permutation entropy (PE) to gain information about the developing influence of the ANS within each fetal state. In this study, 55 magnetocardiograms from healthy fetuses of 24-41 weeks' GA were recorded for up to 45 min using a fetal biomagnetometer. Fetal states were classified based on HRV and movement detection. HRV parameters were calculated for each state. Before GA 32 weeks, 58.4% quiescence and 41.6% activity cycles were observed. Later, 24% quiet sleep state (1F), 65.4% active sleep state (2F), and 10.6% active awake state (4F) were observed. SDNN increased over gestation. Changes of HRV parameters between the fetal behavioral states, especially between 1F and 4F, were statistically significant. Increasing fetal activity was confirmed by a decrease in PE complexity measures. The fHRV parameters support the differentiation between states and indicate the development of autonomous nervous control of heart rate function.

The effect of routine magnesium supplementation on fetal cardiac time intervals: a fetal magnetocardiographic study.

OBJECTIVES: Magnesium deficiency in pregnancy is frequent, and in consequence magnesium supplementation is widely used. As magnesium crosses the placental barrier and since the fetal kidney does not excrete magnesium as efficiently as the mature kidney, effects on fetal cardiac time intervals are probable, but still unknown. STUDY DESIGN: Sixty pregnant women were included in an observational study: 31 patients received oral routine magnesium supplementation. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate electrophysiological rhythm patterns with high temporal resolution. fMCG tracings were analyzed according to a predefined procedure for fetal cardiac time interval (CTI)-detection. fCTI findings (P-wave, PQ-segment, PR-interval, QRS complex, ST segment, T-wave and QTc interval) were registered. RESULTS: Significant widening of the QRS-complex (p=0.004) was demonstrated in fetuses whose mothers received magnesium supplementation (240 mg/day) relative to the control group. CONCLUSION: Magnesium exposed fetuses demonstrated a prolonged ventricular arousal, but healthy neonatal outcome was found in all exposed fetuses. Although fMCG is a preclinical method and limited in its availability, the procedure could help to monitor fetuses.