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Previous reports from this laboratory have demonstrated evidence for synthesis and release of acetylcholine (ACh) and catecholamines (CAs) by human amniotic epithelial cells (HAEC) and the presence of ACh and CAs in amniotic fluid. To study the physiological role of amniotic ACh, we used an experimental pregnant rat model for intrauterine growth retardation. Prior to this experiment, we confirmed the presence of choline acetyltransferase in the HAEC by immunocytochemical staining. Amniotic fluid was collected at 48 and 72 h after a transient ligation of the uterine vessels near the lower and upper ends of the right horn of the pregnant rat. The ACh concentration in the amniotic fluid from rats received intrauterine ischemia increased with time to a greater degree compared with the control rat, although the increase was not statistically significant. These results suggest that intrauterine hypoxic conditions cause a tendency to increase ACh concentrations in the amniotic fluid. [Copyright &y& Elsevier]

Abstract: Objective: Our objective was to examine whether heart rate time series of healthy normal fetuses possess fractal properties and, if so, to determine whether consistent changes in fractal features according to gestational age exist. Design of the study: One hundred nineteen fetal heart rate (FHR) recordings in 55 singleton pregnancies between the 22nd and 41st weeks were analyzed. Fractal analysis developed by Higuchi was performed. Changes of fractal dimension were examined according to gestational age. Results: Two characteristic scaling regions were present in each FHR trace. The fractal dimension defined within 500 ms to 5 s (D S; median 1.396, range 1.273–1.642) was lower than that defined longer than 30 s (D L; median 1.933, range 1.492–2.049) in every case. These two values were significantly different (p <0.001). There was a statistically significant difference in the values of D S between (22–29 weeks, mean 1.323), (30–33 weeks, mean 1.443) (p =0.004), (34–35 weeks, mean 1.418) (p =0.002), (36 weeks, mean 1.409) (p =0.030), (37–38 weeks, mean 1.394) (p =0.006), and (40–41 weeks, mean 1.452) (p =0.001), respectively. D S values between (40–41 weeks), (37–38 weeks) (p =0.012), and (39 weeks, mean 1.369) (p =0.030), respectively, were also significantly different. The values of D L decreased from 22–39 weeks (median 1.941) to 40–41 weeks (median 1.891) (p =0.008). Conclusions: Two distinct fractal structures within the FHR variation were identified. Fractal features of heart rate of healthy normal fetuses change significantly during pregnancy period. Fractal analysis may be useful for evaluating FHR variation. [Copyright &y& Elsevier]

Abstract: Background: Very premature infants occasionally have neurodevelopmental disabilities. However, there have been quite limited data on prenatal risk factors associated with their neurodevelopmental outcomes. Aim: To clarify the relationship between prenatal risk factors and neurodevelopmental outcomes of very premature infants. Study design: The study design is a retrospective review. Subjects: One hundred seventy Japanese women with a singleton pregnancy and their infants whose birth weight being less than 1500g were included. We classified those infants into 118 appropriate for gestational age (AGA) and 52 small for gestational age (SGA) infants. Outcome measures: Infants'' neurodevelopmental outcomes at 18months of corrected age were evaluated by the Kyoto Scale of Psychological Development 2001 (KSPD). We analyzed and compared the infants'' outcomes and prenatal risk factors between two groups. Results: Mortality and rate of infants unevaluable by KSPD because of severe impairment were not significantly different between those groups. However, the developmental quotient score of the cognitive–adaptive area in SGA infants born between 25 and 31weeks of gestation was significantly lower than that in AGA infants randomly selected as gestation-matched controls. More advanced gestational age and heavier birth weight protected against adverse neurodevelopmental outcomes in both groups. Moreover, male infants were related to the excess risk of adverse neurodevelopmental outcomes in the SGA group. Conclusion: In view of the neurodevelopment of the infants, it seems that the most efficient obstetric strategy for improving prognosis of premature infants should be targeted to prolong the pregnancy period as long as the reassuring fetal status and maternal stable health condition are being confirmed. [Copyright &y& Elsevier]

Abstract: Background: Many studies on the physiology of the cardiovascular system reported that nonlinear chaotic dynamics may govern the generation of the heart rate signal. Objective: To examine whether the heart rate dynamics of an intrauterine growth restricted (IUGR) fetus is different from a healthy normal fetus by nonlinear methods of time series analysis. Design of the study: One hundred nineteen fetal heart rate (FHR) recordings from healthy normal fetuses, and 69 recordings from IUGR fetuses were analyzed. Nonlinear analyses included attractor reconstruction, calculation of the largest Lyapunov exponents using the Wolf algorithm, and estimation of correlation dimension. The largest Lyapunov exponents from normal fetuses were checked by means of surrogate-data test. Results: Abnormal FHR patterns of IUGR fetuses such as decreased variability and repetitive late decelerations presented a remarkably different structure in the reconstructed attractor. Surrogate data suggest that the FHR of healthy normal fetuses has unique nonlinear characteristics. The largest Lyapunov exponents were positive for all of 119 healthy normal fetuses, indicating that the FHR control system is sensitive to initial conditions. The values of IUGR fetuses were significantly lower than those of normal subjects. In normal fetuses, significant changes of correlation dimension according to gestational age were observed. In IUGR fetuses, however, such changes were not found. Conclusions: The heart rate dynamics of IUGR fetuses is less chaotic than that of normal fetuses. Decreased system complexity suggested by correlation dimension may limit the IUGR fetuses'' ability to maintain cardiovascular integrity, and therefore, to adapt to the variety of internal and external cardiovascular stresses. [Copyright &y& Elsevier]