Successful detection of the fetal electrocardiogram waveform changes during various states of singletons.

Accurate assessment of fetal well-being is one of the most important tasks for obstetricians. It is still difficult to measure fetal electrocardiogram (ECG) during fetal movements. Recently, a new method, blind source separation with reference signals, was proposed for stable measurements. This method distinguishes weak signals from noisy mixed signals with little information about the sources. The aim of this study is to estimate the ability of this method for fetal ECG monitoring and to establish standard fetal ECG electrocardiogram values of normal singletons including during fetal movement. The subjects enrolled were 167 pregnant women with normal single pregnancy from 18- to 41-week gestation, who regularly visited Tohoku University Hospital, and 12 pregnant women with fetal abnormality. Fetal signals were successfully separated in 163 of 179 subjects at 91.1% success rate regardless of fetal movements. Time intervals of ECG (P, PR and QRS intervals and QTc) were measured. The standard curves of each interval through the gestational period were obtained. The data in active phase were compared to that in rest phase and the data obtained from normal and abnormal fetuses were investigated. PR intervals in the rest phase were prolonged compared to those in the active phase. Fetal ECG showed anomalous values such as PR interval or QTc prolongation in the abnormal fetuses. The fetal ECG was measured by the new method with or without fetal movements, and the standard fetal ECG values have been established. This study provides a foundation for further detailed clinical studies.

Maternal undernutrition with vaginal inflammation impairs the neonatal oligodendrogenesis in mice.

Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.

Understanding congenital heart defects through abdominal fetal electrocardiography: case reports and clinical implications.

AIMS: Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings. MATERIAL & METHODS: This is a report of four cases of prenatally diagnosed congenital heart defects seen at a university hospital in Sendai, Japan. Their complete and thorough evaluation included, among other tests, abdominal FECG analysis. RESULTS: The presence of premature ventricular contractions, a prolonged pre-ejection period (PEP > 75 msec), and prolonged QTc intervals (QTc > 440 msec) served as markers of hemodynamic alteration but were unlikely determinants of disease severity precluding further investigation. CONCLUSIONS: In practice, similar findings found on FECG should raise the index of suspicion for the presence of congenital heart disease and prompt a targeted ultrasound scan.

Effects of antenatal steroid therapy on neurodevelopment in an IUGR mouse model.

BACKGROUND/OBJECTIVE: To investigate the neurodevelopmental response in postnatal mice secondary to antenatal steroid treatment in association with maternal protein restriction. METHODS: C57BL/6N pregnant mice (n = 24; 4 per treatment group) were administered control (C) or protein-restricted (PR) diets and subjected to daily subcutaneous injection stress during late gestation (E10-E17) with either 100 microl/kg of dexamethasone sodium phosphate in normosaline (C-D/S, PR-D/S) or normosaline alone (C-S, PR-S). Non-treatment groups were also included (C, PR). Brain samples of pups were collected on postnatal day 7 and analyzed by immunohistochemistry and qRT-PCR. RESULTS: Neonatal weights in the treatment groups were smaller than their counterparts in the C group, but there were no significant differences in brain size. Immunohistochemical evaluation of neuroglial cells revealed a pronounced effect of protein restriction on oligodendrocytes and oligodendrocyte precursor cells with distinct fetal responses to stress and dexamethasone. Further evaluation using quantitative RNA analysis showed significant activation of Galr1, Galr2, Igfbp-1, Igfbp-3, Igfbp-6, and Fgf2 by 1- to 2.5-fold in the PR-D/S group and by much higher increments, 1- to 10.5-fold, in the PR-S group. CONCLUSION: This preliminary investigation revealed the possible role of dexamethasone in further increasing vulnerability to cell damage in injury-prone neuroglial cells. The distribution of key glial markers and the overexpression of several neurotrophic factors depicted ongoing cellular adaptation.

The uterus sustains stable biological clock during pregnancy.

Maternal circadian information has been reported to play an important role in fetal physiology and development. Hormones and nutrition have been mainly investigated as circadian cues from mother to fetus. However, the influences of circadian properties of the pregnant reproductive organs on fetuses have not been fully investigated. To gain an insight on the circadian functions of the reproductive organs, we examined molecular clocks in the pregnant rat uterus and placenta. By using a Period1-luciferase (Per1-luc) rat, whose tissues express luciferase corresponding to activation of Period1, a "key clock gene", we examined the uterus clock during non-pregnancy, on embryonic day 12 (E12), and on E22 (the end of pregnancy) in a light-dark (LD) cycle and constant darkness (DD). By in situ hybridization we further explored Per1 mRNA rhythms in the placenta on E12 and E22. The uterus in vitro showed clear circadian Per1-luc rhythms both in and out of pregnancy, having peaks at around the time corresponding to dusk in LD. Likewise, in DD, the uterus in vitro had the same Per1-luc rhythms. The decidua in LD showed circadian Per1 mRNA rhythms, peaking during night 6 h after dusk, while the decidua in DD showed the same Per1 mRNA rhythms only on E22. In contrast, the labyrinth showed no circadian Per1 mRNA rhythms in LD or DD during pregnancy. These results suggest that the uterus and decidua, a maternally-originated tissue of the placenta, but not the labyrinth, a fetus-originated tissue of the placenta, can provide the fetus with circadian information.

Maternal feeding controls fetal biological clock.

BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD) cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN) and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.

Prediction of preterm birth in symptomatic women using decision tree modeling for biomarkers.

OBJECTIVE: The objective of the study was to use recursive partitioning (RP) to identify gestational age-specific and threshold values for infectious and endocrine biomarkers of imminent delivery. STUDY DESIGN: RP was developed using a previously collected data set and then applied to a prospectively collected cohort of women in threatened preterm labor. Predictors of preterm birth were considered, including white blood cell count (WBC), corticotrophin-releasing hormone (CRH), cortisol, and maternal age. RESULTS: At 22-27 weeks' gestation, WBC of greater than 12,000/mL was the most accurate predictor of delivery within 48 hours; at 28-31 weeks' gestation, CRH of greater than 684 pg/mL was the most accurate predictor; and at 32-26 weeks' gestation, CRH and maternal age were the most important variables. CONCLUSIONS: These results indicate that maternal WBC greater than 12,000/mL prior to 28 weeks' gestation and CRH beyond 28 weeks are the most accurate biomarkers in predicting preterm birth within 48 hours. RP assists in establishing clinically relevant and gestational age-specific threshold levels for these variables.

Effect of the interaction between lipoxygenase pathway and progesterone on the regulation of hydroxysteroid 11-Beta dehydrogenase 2 in cultured human term placental trophoblasts.

Placental hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2) plays an important role in pregnancy maintenance and fetal maturation. In the event of intrauterine infection, lipoxygenase (LOX) metabolites are produced in the placenta and contribute to preterm labor and adverse fetal outcomes. On the other hand, LOX metabolites are involved in production of progesterone, which is required for pregnancy maintenance. In this study, we evaluated the interaction between the LOX pathway, progesterone, and HSD11B2. Specifically, we hypothesized that LOX metabolites would alter HSD11B2 and this effect would be mediated by progesterone. We cultured human term placental trophoblasts in the presence and absence of the LOX inhibitors Nordihydroguaiaretic acid (NDGA), AA861, and Baicalein; the LOX metabolites Leukotriene B(4) and 12(S)-Hydroxyeicosatetraenoate (12-HETE); and progesterone and progesterone receptor antagonist RU486. By radiometric conversion assay, real-time quantitative PCR, Western blot analysis, and ELISA, we examined HSD11B2 enzyme activity, HSD11B2 mRNA and HSD11B2 protein expression, and progesterone output. LOX metabolites down-regulated HSD11B2 activity and HSD11B2 expression. LOX inhibitors up-regulated HSD11B2 activity and HSD11B2 and HSD11B2 expression, and these effects were attenuated by addition of LOX metabolites. Net progesterone output was increased by LOX metabolites and decreased by LOX inhibitors. Progesterone down-regulated HSD11B2 activity and HSD11B2 and HSD11B2 expression, and these effects were blocked by RU486. Furthermore, the suppressive effect of 12-HETE on HSD11B2 activity was also reversed by RU486. We conclude that HSD11B2 in human placental trophoblasts is decreased by progesterone and increased by inhibition of endogenous LOX metabolites, and that a component of the effect of LOX metabolites on HSD11B2 is mediated by their stimulation of endogenous progesterone output.

Fetal myocardial thickening measured by ultrasonic-based technique called 'phased-tracking method'.

OBJECTIVE: To evaluate fetal myocardial movement by using newly developed ultrasonic technique. METHODS: We analyzed 50 normal fetuses between 25 and 41 weeks' gestation for changes in thickness of fetal myocardium using the phased-tracking method, a technique with high vertical distance resolution and the potential to evaluate fine ventricular wall movements. We analyzed differences in the rate of change in ventricular wall thickness and in changes in the inner and outer wall layers with advancing gestation. We also analyzed myocardial thickening period and evaluated the ratio of increasing thickness period to stroke interval. RESULTS: Mean thickness changing rate was significantly higher in the right (1.18 +/- 0.34 m/s/m) than in the left ventricular wall (0.86 +/-0.31 m/s/m) (p < 0.001). Mean ratio of increasing thickness period to stroke interval was significantly higher in the right (0.57 +/- 0.064) than in the left ventricle (0.46 +/- 0.075) (p < 0.001), indicating that myocardial contraction in the fetal right ventricle predominates. The thickness-changing rate of the bilateral ventricular walls was positively and linearly correlated with gestational age. The myocardial-wall thickness-changing rate was higher in the outer layer than in the inner layer in late gestation. CONCLUSIONS: We conclude that measurement of the thickness-changing rate of fetal ventricular walls using the phased-tracking method might be useful for evaluation of fetal cardiac function.

Clinical manifestations and outcomes of parvovirus B19 infection during pregnancy in Japan.

Parvovirus B19 is a small DNA virus. Infection with parvovirus B19 during pregnancy may cause serious complications in the fetus, including hydrops fetalis and fetal death. The purpose of the present study is to clarify the clinical manifestations and outcomes of parvovirus B19 infection during pregnancy. This prospective study enrolled 478 women with suspected B19 infections during pregnancy between 1999 and 2004. One hundred cases (21%) of B19 infection were detected in 478 pregnant women who had been exposed to B19. Serological infection was confirmed by measurement of B19-specific IgM and IgG in sera. Forty-nine cases reported maternal clinical symptoms and 51 cases were asymptomatic. Facial rash was the most common symptom, with 51% (25/49) of the symptomatic patients complaining of either a facial, body or limb rash. The most common infectious source was children living in the home. Overall, the incidence of adverse fetal effects (including hydrops fetalis and fetal death) related to intrauterine B19 infection was 7% (7/100), and all seven cases were exposed to B19 infection before 20 weeks of gestation. Although half of the cases with parvovirus B19 infections during pregnancy were asymptomatic, patients with adverse fetal effects tended to be symptomatic including rash and fever. These clinical data may supply useful information to produce clinical guidelines for managing B19 infection during pregnancy.

Appearance of abnormal electrocorticogram patterns during umbilical cord compression in sheep fetus.

A frequent cause of fetal acidemia, which sometimes results in hypoxic-ischemic encephalopathy, is umbilical cord compression associated with uterine contraction. Using a sheep model of fetal acidemia, we examined the changes in electrocorticogram (ECoG), carotid artery blood flow, arterial blood pressure and fetal heart rate during cord compression. A characteristic burst of ECoG spikes emerged during cord compression at fetal arterial pH 7.18 even before the pH went down to severe fetal acidemia (less than 7.10). The administration of a neuromuscular blocking agent to the fetus did not abolish the appearance of the spikes. These results suggest that cord compression may cause abnormal brain excitement even in the absence of severe fetal acidemia and that this abnormal excitement can lead to fetal brain dysfunction, if cord compression is repeated or prolonged.

Effect of pro-inflammatory cytokines on expression and activity of 11beta-hydroxysteroid dehydrogenase type 2 in cultured human term placental trophoblast and human choriocarcinoma JEG-3 cells.

OBJECTIVE: 11Beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is thought to act as a placental barrier protecting the fetus from high levels of maternal cortisol. On the other hand, intrauterine infection is one of the main causes of preterm birth and adverse fetal outcome, and pro-inflammatory cytokines may contribute to these adverse effects. However, the effect of pro-inflammatory cytokines on 11beta-HSD2 is still not clear. Therefore, we have evaluated the effect of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on 11beta-HSD2 in cultured human placental trophoblast and in human choriocarcinoma JEG-3 cells. METHODS: Placental trophoblast cells were isolated from human term placenta. Placental trophoblast cells and JEG-3 cells were treated with TNF-alpha (0.1-10 ng/mL) or IL-1beta (0.1-10 ng/mL). Real-time reverse transcription polymerase chain reaction and Western blot were used to study the regulation of 11beta-HSD2 expression. 11beta-HSD2 activity was determined by measuring the rate of cortisol to cortisone conversion in the culture medium using thin-layer chromatography (TLC). RESULTS: In placental trophoblast, TNF-alpha and IL-1beta down-regulated 11beta-HSD2 mRNA expression and activity (both P <.05). The protein level was decreased only with IL-1beta (P <.05). In JEG-3 cells, 11beta-HSD2 mRNA was decreased by TNF-alpha but up-regulated by IL-1beta, with no significant change in protein expression and activity. CONCLUSION: Our results suggest caution in interpreting data using JEG-3 cells. However, our studies with primary trophoblast suggest that TNF-alpha and IL-1beta may increase the amount of cortisol crossing to the placenta and fetal circulation by attenuating 11beta-HSD2 activity, potentially contributing to preterm labor and altered fetal outcome in uterine infection.

Decrease and senescence of endothelial progenitor cells in patients with preeclampsia.

BACKGROUND: In preeclampsia, the precise mechanism of impaired vascular function is still unclear. We hypothesized that cellular function of circulating endothelial progenitor cells (EPCs) might be impaired in patients with preeclampsia. OBJECTIVE: The objective of this study was to investigate the number and status of cellular senescence of EPCs in the circulation of women with preeclampsia. METHODS: Circulating EPCs were cultured from patients with preeclampsia (n = 8) and normotensive pregnant women (n = 7). EPC numbers were assessed by colony-forming unit (CFU) methodology as previously reported. In addition, to assess cellular senescence, we measured endogenous beta-galactosidase activity. Moreover, we assessed whether the serum level of C-reactive protein (CRP), a marker for systemic inflammation, was associated with cellular impairment of EPCs. RESULTS: The number of circulating EPCs was decreased in women with preeclampsia controls (median, 10.0 vs. 34.0 CFU; P < 0.01). The rate of cellular senescence was significantly increased in patients with preeclampsia (33.9%) compared with that in controls (22.9%; P < 0.05). Patients with preeclampsia were divided into two subgroups: the CRP-negative group (CRP, <0.1 mg/dl; n = 4) and the CRP-positive group (CRP, > or =0.1 mg/dl; n = 4). Interestingly, EPC CFU counts were markedly decreased in CRP-positive patients compared with those in CRP-negative patients (5.0 and 25.0 CFU, respectively; P < 0.05). Median values for cellular senescence were greater in the CRP-positive group than in the CRP-negative group, although this did not achieve statistical significance (43.5% and 33.3%, respectively; P = 0.12). CONCLUSION: Depletion and cellular aging of EPCs in patients with preeclampsia might be associated with endothelial dysfunction and could be affected by systemic inflammation.

Successful conservative treatment of a cesarean scar pregnancy with uterine artery embolization.

Ectopic pregnancy developing in a previous Cesarean section scar is rare and is associated with catastrophic complications, such as uterine rupture and uncontrollable bleeding, which may lead to loss of the uterus. The operative treatments that have been reported for cesarean scar pregnancy are dilatation and curettage and excision of trophoblastic tissues using either laparotomy or laparoscopy. Recently, conservative treatment of scar pregnancy with locally and/or systemically administered methotrexate (MTX) has been reported. However, recent reports demonstrated that cases treated with MTX sometimes required laparotomy later because of excessive bleeding. In this series of cases we have demonstrated that viable cesarean scar pregnancies can be treated safely by selective transarterial embolization in combination with subsequent dilatation and curettage and local or systemic injections of MTX. In these three cases, uterine artery embolization proved to be a useful procedure for preventing uncontrollable bleeding and unnecessary uterine loss.

Clinical evaluation of the risk of twin-to-twin transfusion syndrome using the relative power contribution of fetal heart rate fluctuations.

OBJECTIVES: In twin pregnancies, it has been suggested that fluctuations of the two fetal heart rates should be considered as two variates that affect each other. We therefore investigated whether the relative power contribution (RPC) of heart rate fluctuation between twins reflects the clinical severity of twin-to-twin transfusion syndrome. STUDY DESIGN: Sixty-three cases of twin pregnancy including 43 monochorionic twins and 20 dichorionic twins were studied. Thirteen monochorionic twins with polyhydramnios in one twin were regarded as twin-to-twin transfusion syndrome (TTTS). Of the 13 TTTS cases, 8 cases with polyhydramnios in one twin and oligohydramnios in the other were deemed to be a 'stuck' twin. The RPC of the very low frequency domain (VL; 0.0125-0.0625 Hz) of fetal heart rate fluctuation in the twin fetuses of monochorionic and dichorionic pregnancies was obtained within a week of delivery. The relationship between the value of the RPC and the outcome of these twins was examined. RESULTS: For both monochorionic and dichorionic twins the RPC of twin fetuses was significantly higher in TTTS twins than in twins without TTTS. In particular, in pregnancies that resulted in fetal death, early neonatal death, or hydrops of one of the twins, this twin had a higher RPC than the other twin. No significant difference was observed in the RPC value between twins of either monochorionic or dichorionic pregnancies that did not develop TTTS. Serial changes in RPC values were followed in 7 cases of TTTS. The RPC value rose rapidly just before delivery in three cases with resultant poor outcome. CONCLUSION: A rapid change in the RPC of twin fetuses measured using the VL frequency domain of fetal heart rate fluctuations may predict poor outcome in twin pregnancies.

Parvovirus B19 and the pathogenesis of anaemia.

Human parvovirus B19 (B19) infection causes human bone marrow failure, by affecting erythroid-lineage cells which are well-known target cells for B19. The anaemia induced by B19 infection is of minor clinical significance in healthy children and adults, however, it becomes critical in those afflicted with haemolytic diseases. This condition is called transient aplastic crisis, and the pathogenesis is explained by the short life-span of red blood cells. Similarly, fetuses are thought to be severely affected by B19-intrauterine infection in the first and second trimester, as the half-life of red blood cells is apparently shorter than RBC at the bone marrow haematopoietic stage. On the other hand, B19 is also the causative agent of persistent anaemia in immunocompromised patients, transplant recipients and infants. The deficiencies of appropriate immune responses to B19 impair viral elimination in vivo, which results in enlargement of B19-infected erythroid-lineage cells. The B19-associated damage of erythroid lineage cells is due to cytotoxicity mediated by viral proteins. B19-infected erythroid-lineage cells show apoptotic features, which are thought to be induced by the non-structural protein, NS1, of B19. In addition, B19 infection induces cell cycle arrests at the G(1) and G(2) phases. The G(1) arrest is induced by NS1 expression prior to apoptosis induction in B19-infected cells, while the G(2) arrest is induced not only by infectious B19 but also by UV-inactivated B19, which lacks the ability to express NS1. In this review, we address the clinical manifestations and molecular mechanisms for B19-induced anaemia in humans and a mouse model, and of B19-induced cell cycle arrests in erythroid cells.

Establishment of multifunctional monoclonal antibody to the nonstructural protein, NS1, of human parvovirus B19.

OBJECTIVES: NS1 expression of human parvovirus B19 is a critical event in B19 pathogenesis. However, the mechanisms of NS1-induced cytotoxicity in B19 infection have yet to be clarified mainly because of the absence of multifunctional monoclonal antibodies (Mab) against NS1. The purpose of this study was to establish such Mab, which function in immunoprecipitation assays, immunoblotting, indirect immunofluorescence, and immunohistochemical staining. METHODS: Balb/c mice were immunized with the recombinant NS1 protein and hybridoma cell lines producing Mab against the NS1 protein were screened by ELISA, immunoprecipitation, immunoblotting, and indirect immunofluorescence staining. The Mab were used for immunohistochemical staining of formalin-fixed tissues from an intrauterine B19 infected fetus. RESULTS: ParC-NS1, the monoclonal antibody against the NS1 protein, worked in all tested screening methods. ParC-NS1 could also detect NS1 protein expressed in clinical tissue specimens. CONCLUSIONS: The ParC-Ns1 monoclonal antibody was specific against the NS1 protein. In addition, NS1 protein expression was successfully identified in human tissues. These data indicated that this monoclonal antibody should be a useful tool to study the kinetics and sites of NS1 expression and NS1-induced cytotoxicity in B19 infection.

Fractal and periodic heart rate dynamics in fetal sheep: comparison of conventional and new measures based on fractal analysis.

The physiological significance of spectral and fractal components of spontaneous heart rate (HR) variability in the fetus remains unclear. To examine the relationship between circadian rhythms in different measures of HR variability, R-R interval time series obtained by fetal ECGs were recorded continuously over 24 h in five pregnant sheep at 116-125 days gestation. Conventional measures of short-term (STV) and long-term variability (LTV), low-frequency (LF; 0.025-0.15 cycles/beat) and high-frequency (HF; 0.2-0.5 cycles/beat) spectral powers, the LF-to-HF ratio, and fractal dimension values were calculated from 24-h ECG recordings and quantified every 60 min. STV, LTV, and LF and HF spectral powers were minimal during the day but increased significantly to their highest values at night. We found a significant positive correlation between these measures, whereas the cosinor method showed significant similarity between their circadian rhythm patterns. Fetal R-R intervals also exhibited fractal structures. Fetal HR variability had a fractal structure, which was similar between day and night. These results suggested that the circadian rhythms exhibited by STV and LTV during the day were mainly due to changes in frequency components rather than to fractal components of fetal HR fluctuation.