Jeong-Kyu Hoh

Comparison of fetal heart rate patterns using nonlinear dynamics in breech versus cephalic presentation at term

BACKGROUND It has been reported that breech fetuses have inferior neurological outcomes regardless of mode of delivery, raising the possibility that in utero neurological impairment is more frequent in breech fetuses, possibly contributing to malpresentation. AIMS To assess differences between the cardiovascular autonomic nervous systems (ANSs) of breech and cephalic fetuses using nonlinear dynamic indices of fetal heart rate (FHR) variability. STUDY DESIGN AND SUBJECTS This study included 86 fetuses with breech presentation and 173 fetuses with cephalic presentation, with no other maternal or fetal problems. We analyzed FHR variability and spectral indices as markers of ANS behavior. We used nonlinear dynamic indices to represent the complexity of heart rate regulation, as well as correlation dimension as a chaotic index of the cardiovascular control system. RESULTS One of FHR parameters (Mean minute range) was significantly lower in breech than cephalic fetuses (p=0.0294). However, there were no other significant differences in any linear or nonlinear indices, nor in clinical outcomes, between breech and cephalic fetuses. CONCLUSION Our data suggest that breech fetuses have neither more active ANS nor less active complexity control systems than do cephalic fetuses. This indicates that the neurologic maturation of breech fetuses is not inferior to cephalic ones. The practical implication of these findings is that the nervous system integrity of breech fetuses may not result directly in neonatal complications.

Computerized fetal heart rate monitoring after vibroacoustic stimulation in the anencephalic fetus.

BACKGROUND To quantify changes in fetal heart rate (FHR) parameters after vibroacoustic stimulation (VAS) and to evaluate the usefulness of VAS testing (VAST) in anencephalic fetuses. Our findings may also help to clarify the route(s) of vibration and sound transmission during VAST. STUDY DESIGN AND SUBJECTS We obtained the antepartum FHR tracings of 16 anencephalic fetuses, including both the nonstress test (NST) and VAST. Using a computerized monitoring system, HYFM, we determined all FHR parameters from data collected for 10 min before and 10 min after VAS, at successive gestational stages. RESULTS We observed three false reactive responses at term. The false reactive rate for VAST (3/16) was higher than that for NST (1/16). No FHR parameters increased significantly after VAS except for the number of fetal movements (FM), which increased significantly in all gestational groups (25th-32nd and 33rd-40th weeks). CONCLUSIONS These findings call attention to an increased probability of a false reactive response in VAST analysis, when the fetus is affected by a CNS disorder. Increased numbers of FM after VAS suggest that the vibratory pathway is more likely to elicit fetal response than the auditory pathway in this setting, and that the vibratory stimulation travels by subcortical rather than by cortical pathways.

Determination of fetal heart rate reactivity from a single 20-min window of non-stress testing in compromised fetuses.

Abstract Aims: To shorten the analysis time needed for non-stress testing (NST) without decreasing efficacy in compromised fetuses. Methods: We selected 80 cases with a 5-min Apgar score <7 as a study group and 259 cases with a 5-min Apgar score ≥9 as a control group. We applied four different criteria (A, B, C, and D) to each study and control group for the first 20-min window of NST data to evaluate reactivity. Criteria A, B, and C consisted of conventional reactivity criteria according to amplitude (15 or 10 beats per minute), duration (15 or 10 s) and weeks of gestation (≤31, ≥32), and criteria D combined criteria C with approximate entropy (ApEn). Results: The sensitivity of criteria D (91.25%) was greater than the other three criteria (P<0.0001). The specificities of criteria C (96.14%) and D (99.23%) were also higher than criteria A and B (P<0.0001). The positive and negative predictive value of criteria D were better than that of criteria C (97.33 vs. 83.87, P=0.0066) and (97.35 vs. 89.89, P=0.0004), respectively. Conclusion: Adding ApEn to the conventional criteria for reactivity shortened NST analysis time without decreasing efficacy, facilitating a decision of reactivity within a single 20-min NST window.

Sex-related differences in the development of fetal heart rate dynamics

BACKGROUND Despite previous efforts to explain the general advantages of female fetuses over males regarding health, sex-related differences in the dynamics or complexity of fetal heart rate (FHR) variability and FHR maturation patterns have not yet been identified. AIM To make linear and nonlinear comparisons of antepartum FHR indices, dynamics, complexity, and reactivity to the non-stress test (NST) and vibroacoustic-stimulation test (VAST) in male and female fetuses. STUDY DESIGN A total of 3835 singleton term deliveries without maternal and fetal complications were divided into female (n=1849) and male (n=1986) groups, and subjected to comparison and analyses. SUBJECTS Linear FHR indices, approximate entropy (ApEn), sample entropy (SampEn), short-term/long-term exponents (α1/α2), correlation dimension (CD), NST and VAST criteria, and modified nonlinear reactive criteria (MNRC) were used to evaluate outcomes. RESULTS ApEn was consistently higher in female fetuses than in male ones. ApEn in female fetuses was maximal at 29-30 gestational weeks, while the increase in ApEn was delayed in male fetuses but more rapid, reaching its peak at 31-32 gestational weeks. In both sexes, CD increased up to term, and α2 rapidly decreased up to 31-32weeks in an analogous manner. The two sexes differed significantly in response to VAST at <31 gestational weeks and there was a structural difference in reactive patterns under MNRC. CONCLUSIONS Female fetuses exhibit greater heart rate dynamics in early gestational periods, suggesting that their cardiovascular system matures earlier than that of males. Male fetuses undergo a compensatory period of rapid change to catch up with females at term.

Estimating time to full uterine cervical dilation using genetic algorithm

The objectives of this study were to provide new parameters to better understand labor curves, and to provide a model to predict the time to full cervical dilation (CD). We studied labor curves using the retrospective records of 594 nulliparas, including at term, spontaneous labor onset, and singleton vertex deliveries of normal birth weight infants. We redefined the parameters of Friedmans labor curve, and applied a three‐parameter model to the labor curve with a logistic model using the genetic algorithm and the Newton–Raphson method to predict the time necessary to reach full CD. The genetic algorithm is more effective than the Newton–Raphson method for modeling labor progress, as demonstrated by its higher accuracy in predicting the time to reach full CD. In addition, we predicted the time (11.4 hours) to reach full CD using the logistic labor curve using the mean parameters (the power of CD = 0.97 cm/hours, a midpoint of the active phase = 7.60 hours, and the initial CD = 2.11 cm). Our new parameters and model can predict the time to reach full CD, which can aid in the forecasting of prolonged labor and the timing of interventions, with the end goal being normal vaginal birth.

Noggin Over-Expressing Mouse Embryonic Fibroblasts and MS5 Stromal Cells Enhance Directed Differentiation of Dopaminergic Neurons from Human Embryonic Stem Cells

Directed methods for differentiating human embryonic stem cells (hESCs) into dopaminergic (DA) precursor cells using stromal cells co-culture systems are already well established. However, not all of the hESCs differentiate into DA precursors using these methods. HSF6, H1, H7, and H9 cells differentiate well into DA precursors, but CHA13 and CHA15 cells hardly differentiate. To overcome this problem, we modified the differentiation system to include a co-culturing step that exposes the cells to noggin early in the differentiation process. This was done using γ-irradiated noggin-overexpressing CF1-mouse embryonic fibroblasts (MEF-noggin) and MS5 stromal cells (MS5-noggin and MS5-sonic hedgehog). After directed differentiation, RT-PCR analyses revealed that engrailed-1 (En-1), Lmx1b, and Nurr1, which are midbrain DA markers, were expressed regardless of differentiation stage. Moreover, tyrosine hydroxylase (Th) and an A9 midbrain-specific DA marker (Girk2) were expressed during differentiation, whereas levels of Oct3/4, an undifferentiated marker, decreased. Immunocytochemical analyses revealed that protein levels of the neuronal markers TH and TuJ1 increased during the final differentiation stage. These results demonstrate that early noggin exposure may play a specific role in the directed differentiation of DA cells from human embryonic stem cells.

Conventional linear criteria with sample entropy in the interpretation of reactive antepartum fetal heart rate tracings.

Objective: To compare the test duration times and rate of nonreactive results between the conventional linear reactive criteria (CLRC) and the modified nonlinear reactive criteria (MNRC) in electronic fetal heart rate (FHR) monitoring. The MNRC are the CLRC with the addition of approximate entropy or sample entropy. Methods: One thousand women with singleton pregnancies between 30 and 37 weeks’ gestation were selected. They visited Hanyang University Hospital for non-stress tests (NSTs). In these patients, FHR tracings were recorded for 50 min including the first and second 20 min of NST and 10 min of vibroacoustic stimulation test. All patients had a reactive NST with CLRC in these antepartum FHR tests. The rate of nonreactive tests and test duration times of these linear and nonlinear criteria were calculated and compared. Results: The rate of nonreactive tests within a 20- and 40-min period with the MNRC (6.8 and 1.2%) was significantly lower than with the CLRC (35.2 and 10.5%, respectively; p < 0.001). To meet the reactive criteria, the mean durations of the MNRC and the CLRC were 11.47 (95% CI, 11.11–11.84) and 18.45 (95% CI, 17.79–19.12) min, respectively (p < 0.001). The MNRC led to a significant reduction in testing time of 37.8% compared to the CLRC. The rate of reactive tests using only sample entropy (0.20), calculated over 5-min segments of FHR tracings, was 88.3% (95% CI, 88.0–88.7). It was close to the results using the MNRC (93.2%) in the 20-min time window. Conclusion:The use of the MNRC significantly reduced the test duration times and decreased the rate of nonreactive tests when compared to the CLRC. It may be useful in providing more rapid and accurate assessment of the fetus in electronic FHR monitoring.

Fetal heart rate parameters and perinatal outcomes in fetuses with nuchal cords

Aim:  The purpose of the present study was to compare and analyze differences in antepartal fetal heart rate (FHR) parameters during pregnancy and pregnancy outcomes in normal fetuses and fetuses with nuchal cord (NC).

Nonlinear analysis of fetal heart rate dynamics in fetuses compromised by asymptomatic partial placental abruption

INTRODUCTION We analyzed fetal heart rate (FHR) parameters, dynamics, and outcomes in pregnancies with asymptomatic partial placental abruption (PPA) compared with those in normal pregnancies. METHODS We examined nonstress test (NST) data acquired from 2003 to 2012 at our institution. Normal pregnancies (N = 170) and PPA cases (N = 17) were matched for gestational age, fetal sex, and mean FHR. NSTs were performed at 33-42 weeks of gestation. FHR parameters obtained from the NST and perinatal outcomes were analyzed using linear methods. Nonlinear indices, including approximate entropy (ApEn), sample entropy (SampEn), short-term and long-term scaling exponents (α1 and α2), and correlation dimension (CD), were used to interpret FHR dynamics and system complexity. The area under a receiver operating characteristic curve (AUC) was used to evaluate the nonlinear indices. RESULTS There were no significant differences in general characteristics and FHR parameters between the PPA and control groups. However, gestational age at delivery, birth weight, 5-min Apgar scores, ApEn, SampEn, and CD were significantly lower in the PPA group than in the control group (P < 0.05). The long-term scaling exponent (α2) and crossover index (α2/α1) of the PPA fetuses were significantly higher than those of the controls (P < 0.01). A multiple regression model showed better performance in predicting PPA (AUC, 0.92; sensitivity 82.35%; specificity, 94.12%). DISCUSSION Nonlinear dynamic indices of FHR in asymptomatic PPA were qualitatively different from those in normal pregnancies, whereas the conventional FHR parameters were not significantly different.

Complex and irregular heart rate dynamics in fetuses compromised by maternal anemia as a high-risk pregnancy

Abstract Aim: To examine how complex and irregular fetal heart rate (FHR) dynamics differ between fetuses of normal pregnancies and those of pregnancies complicated by maternal anemia (MA), and to place this in the context of high-risk pregnancies. Methods: Our study population consisted of 97 pregnant women affected by MA, 118 affected by pregnancy-induced hypertension (PIH), 88 affected by gestational diabetes mellitus (GDM), 53 with preterm premature rupture of membranes (pPROM), and 356 normal pregnancies as controls. We calculated approximate entropy (ApEn), sample entropy (SampEn), and correlation dimension (CD) to quantify irregularity and the chaotic dynamics of each FHR time series. Results: The ApEn in the fetuses of the MA and PIH groups was significantly lower than that of the normal controls (P<0.05). The SampEn was significantly lower in the high-risk groups, except for the pPROM group, than in the normal controls (P<0.05). The CD in the PIH and severe MA groups was significantly lower than that of the normal controls (P<0.05, respectively). In the MA group, the dynamic indices showed a highly significant positive correlation with hemoglobin (Hb) levels (P<0.0001). Conclusion: The decreased complexity and/or irregularity in the FHR from pregnancies with MA may reflect abnormalities in the complex, integrated cardiovascular control. The irregularity and complexity of the FHR increased together with Hb levels in pregnancies with MA. Our data suggest that the integrity of the nervous system in the fetuses compromised by severe MA might result directly in adverse outcomes.