Compliance of Static Stretching and the Effect on Blood Pressure and Arteriosclerosis Index in Hypertensive Patients.

Background: Treatment of high blood pressure is a combination of lifestyle changes and medications, and appropriateexercise therapy is recommended as one of the lifestyle-related changes. Recently, stretching, a low-intensity exercise, was reported to be antihypertensive and effective for improving arteriosclerosis, in addition to aerobic exercise. The present study investigated the short-term effects of continuous stretching and rest-induced rebound on vascular endothelial function in hypertensive patients. Methods: This study was conducted as a single-arm prospective interventional study including patients between 30 and 70 years of age undergoing treatment for hypertension from October 2019 until May 2021. The intervention consisted of six months of daily stretching, one month of rest, and another three months of stretching. We measured arteriosclerosis indices such as cardio ankle vascular index (CAVI), ankle brachial pressure index (ABI) and reactive hyperemia index (RHI), and flexibility at the baseline and one, three, six, seven, and ten months from the baseline. Results: We included a total of ten patients (three males and seven females) with an average age of 60.10 ± 6.05 years. The exercise rate for the entire period was 90% or more, and the anteflexion measurement value improved significantly before and after the intervention (p < 0.001). Blood pressure and CAVI/ABI were well controlled throughout the study period. RHI did not show any significant improvement during the initial six months, and only slightly improved by the third month (p = 0.063). Even after the rest phase and resumption of stretching, RHI remained stable. Conclusions: The compliance of the stretching program we used, evaluated by the exercise implementation rate for the entire period, was 90% or more; therefore, easy to perform and continue by hypertensive patients. However, we did not observe a significant positive effect on arteriosclerosis index or blood pressure in this study.

Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies.

Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease. Two open-label, uncontrolled phase 3 studies evaluated the 52-week safety and efficacy of enarodustat in Japanese anemic patients with chronic kidney disease not on dialysis (n = 132) [SYMPHONY ND-Long study] or on maintenance hemodialysis (n = 136) [SYMPHONY HD-Long study]. The most frequent adverse events were viral upper respiratory tract infection (25.8%) followed by chronic kidney disease (8.3%) in the SYMPHONY ND-Long study, and viral upper respiratory tract infection (49.3%) followed by contusion (16.9%) and diarrhea (16.9%) in the SYMPHONY HD-Long study. The incidence of any adverse events did not increase over time. Mean hemoglobin levels and 95% confidence intervals were maintained within the target range (10.0-12.0 g/dl) over 52 weeks in both studies. The long-term safety and efficacy of enarodustat were confirmed in Japanese anemic patients with chronic kidney disease.

A Phase 3 Study of Enarodustat (JTZ-951) in Japanese Hemodialysis Patients for Treatment of Anemia in Chronic Kidney Disease: SYMPHONY HD Study.

INTRODUCTION: Enarodustat (JTZ-951) is a new oral hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). We conducted a phase 3 study to compare the efficacy and safety of enarodustat with darbepoetin alfa (DA) in Japanese anemic patients with CKD receiving maintenance hemodialysis. METHODS: Subjects receiving maintenance hemodialysis were randomly assigned at a 1:1 ratio to receive oral enarodustat once daily or intravenous DA every week for 24 weeks with dose adjustment every 4 weeks to maintain hemoglobin (Hb) within a target range (≥10.0 to <12.0 g/dL). The primary efficacy endpoint was difference in mean Hb level between arms during the evaluation period defined as weeks 20-24 (noninferiority margin: -1.0 g/dL). Intravenous iron preparations were prohibited during the screening period and during weeks 0-4. RESULTS: The mean Hb level of each arm during the evaluation period was 10.73 g/dL (95% confidence interval [CI]: 10.56, 10.91) in the enarodustat arm and 10.85 g/dL (95% CI: 10.72, 10.98) in the DA arm. The difference in the mean Hb level between arms was -0.12 g/dL (95% CI: -0.33, 0.10), confirming the noninferiority of enarodustat to DA. The mean Hb level of each arm was maintained within the target range during the treatment period. Increased total iron-binding capacity and serum iron and decreased hepcidin were observed through week 4 in the enarodustat arm albeit after switching from erythropoiesis-stimulating agents. No apparent safety concerns of enarodustat were observed compared with DA. DISCUSSION/CONCLUSION: Enarodustat was noninferior to DA for the treatment of anemia in CKD patients receiving maintenance hemodialysis and was generally well tolerated over 24 weeks.

A Phase 3 Study of Enarodustat in Anemic Patients with CKD not Requiring Dialysis: The SYMPHONY ND Study.

INTRODUCTION: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy (noninferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis. METHODS: Erythropoiesis-stimulating agent (ESA)-naïve patients and ESA-treated patients were randomized at a 1:1 ratio to receive enarodustat orally once daily or DA subcutaneously every 2 or 4 weeks for 24 weeks, respectively. Subjects in each arm had dose adjustments every 4 weeks to maintain their hemoglobin (Hb) level within the target range (10 to 12 g/dl). The primary endpoint was the difference in the mean Hb level between arms during the evaluation period defined as weeks 20 to 24 (noninferiority margin: -0.75 g/dl). RESULTS: The mean Hb level during the evaluation period in the enarodustat arm was 10.96 g/dl (95% confidence interval [CI]: 10.84 to 11.07 g/dl) with a difference of 0.09 g/dl (95% CI: -0.07 to 0.26 g/dl) between arms, establishing its noninferiority to DA. Nearly 90% of subjects in both arms maintained a mean Hb level within the target range. Compared with DA, enarodustat was associated with decreased hepcidin and ferritin, and increased total iron-binding capacity. There were no apparent differences in the incidence of adverse events between arms (65.4% [enarodustat], 82.6% [DA]). CONCLUSIONS: The efficacy of enarodustat was comparable to DA in anemic patients with CKD not requiring dialysis. No new safety concerns were identified compared with DA.

Enarodustat, Conversion and Maintenance Therapy for Anemia in Hemodialysis Patients: A Randomized, Placebo-Controlled Phase 2b Trial Followed by Long-Term Trial.

BACKGROUND: Enarodustat (JTZ-951) is an orally available hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin levels in the treatment of anemia associated with chronic kidney disease (CKD). OBJECTIVE: A phase 2b study of enarodustat to assess the hemoglobin (Hb) response, safety, and maintenance dosage was conducted in Japanese anemic patients with hemodialysis-dependent CKD. METHODS: Subjects receiving a stable dose of an erythropoiesis-stimulating agent were randomized to receive once-daily enarodustat at a dose of 2, 4, or 6 mg or placebo in a double-blind manner for 6 weeks (Period 1) followed by 24-week open treatment with enarodustat, adjusted in the range of 2-8 mg to maintain Hb within a target range (10.0-12.0 g/dL; Period 2). RESULTS: Change in Hb from baseline increased with enarodustat dose in Period 1. In Period 2, the proportion of subjects who maintained their Hb level within the target range at the end of treatment was 65.1%. To maintain Hb levels within the target range over the course of Period 2, approximately 80% of subjects required 2 dose adjustments or fewer. Enarodustat decreased hepcidin and ferritin levels, increased total iron-binding capacity, and was generally well tolerated. CONCLUSIONS: Enarodustat corrected and maintained Hb levels in anemic patients with hemodialysis-dependent CKD. Phase 3 studies of enarodustat are currently ongoing.

A Social Program for the Early Detection of Pancreatic Cancer: The Kishiwada Katsuragi Project.

OBJECTIVES: The early-stage pancreatic cancer (e-PC; stage I/II) detection rate is quite low at approximately 25%. The aim of this study was to evaluate the feasibility of a social program (the Kishiwada Katsuragi project) wherein our hospital, which specializes in PC, and primary care medical offices (PMOs) used clinical findings to detect e-PC. METHODS: Patients with a score of ≥2 points on clinical findings were enrolled: symptoms of abdominal pain/back pain (1 point), new-onset diabetes (1 point), high amylase (AMY) and/or pancreaitc AMY (P-AMY) (1 point), high carbohydrate antigen 19-9 (1 point), and ultrasonography (US) findings including direct (e.g., a solid pancreatic tumor) and/or indirect findings (e.g., dilatation of a pancreatic diameter of ≥2.5 mm and/or cystic lesions) (2 points) were evaluated using the protocol for social programs. RESULTS: Between November 2014 and December 2016, 244 patients were enrolled by 41 PMOs as cooperative facilities, and 15 e-PC cases (53.6%) of the 28 PC patients were detected. The mean clinical finding score of the e-PC group (3.13 ± 1.9) was significantly higher than that of the overall non-PC group (2.1 ± 0.4) (p < 0.05). "High AMY/P-AMY" and "symptoms" were significantly more frequent in the e-PC group than in the non-PC group (p < 0.05). Although the sensitivity of direct findings by US was 40.0%, that of indirect-findings was 93.3% in the e-PC group. Nine and 6 of the 15 patients with e-PC were enrolled via general internal medicine offices (GIMs) and other PMOs without GIMs (general surgery, n = 3; urology, n = 2; otolaryngology, n = 1). CONCLUSION: This social program with collaborations between medical centers that specialize in PC and PMOs used clinical findings, suggesting that not only GIMs but also other PMOs and indirect findings by US may play an important role in improving the e-PC detection rate.

3D/4D sonography - any safety problem.

Gray-scale image data are processed in 3D ultrasound by repeated scans of multiple planes within a few seconds to achieve one surface rendering image and three perpendicular plane images. The 4D image is achieved by repeating 3D images in short intervals, i.e. 3D and 4D ultrasound are based on simple B-mode images. During 3D/4D acquisition, a fetus in utero is exposed by ultrasound beam for only a few seconds, and it is as short as real-time B-mode scanning. Therefore, simple 3D imaging is as safe as a simple B-mode scan. The 4D ultrasound is also as safe as a simple B-mode scan, but the ultrasound exposure should be shorter than 30 min. The thermal index (TI) and mechanical index (MI) should both be lower than 1.0, and the ultrasound study is regulated by the Doppler ultrasound if it is combined with simple 3D or 4D ultrasound. Recently, some articles have reported the functional changes of animal fetal brain neuronal cells and liver cell apoptosis with Doppler ultrasound. We discuss cell apoptosis by ultrasound in this report. Diagnostic ultrasound safety is achieved by controlling the output pulse and continuous ultrasound waves using thermal and mechanical indices, which should be <1.0 in abdominal and transvaginal scan, pulsed Doppler, as well as 3D and 4D ultrasound. The lowest spatial peak temporal average (SPTA) intensity of the ultrasound to suppress cultured cell growth is 240 mW/cm2, below which no ultrasound effect has been reported. An ultrasound user must be trained to recognize the ultrasound bioeffects; thermal and mechanical indices, and how to reduce these when they are higher than 1.0 on the monitor display; and guide the proper use of the ultrasound under the ALARA principle, because the user is responsible for ensuring ultrasound safety.

Electroencephalographic studies of eclampsia and pre-eclampsia.

AIMS: To investigate eclampsia and pre-eclampsia electroencephalograms (EEGs) and related animal experiments, and to publish a Japanese article in English. MATERIALS AND METHODS: A two channel EEG system constructed with a self-made vacuum tube amplifier, optical recorder, signal generator, a magic-eye signal monitor and a shield room were prepared by the author. EEGs were recorded in five admitted eclamptic and 35 pre-eclamptic cases before, during and after convulsion until clinical recovery. The hypothalami of female rabbits were stimulated with Kurotsu's electrode, and blood pressure and urinary proteins were studied before and after stimulation. The rabbits cortical and hypothalamic EEGs were studied. RESULTS: Frontal and occipital EEG waves synchronized immediately before and during eclamptic convulsions and during coma. Large δ waves were characteristic during the coma after convulsions. Moderately slow waves were recorded in cases of pre-eclampsia. In animal experiments, hypertension and proteinuria appeared in cases of hypothalamic sympathetic zone stimulation, while there was no change in parasympathetic stimulation. CONCLUSION: Eclamptic convulsion is evoked by synchronization of the whole cortex controlled by a heavily excited hypothalamus. Pregnancy hypertension and proteinuria is caused by the excited sympathetic center of the hypothalamus.

Invention of ultrasonic Doppler fetal actocardiograph and continuous recording of fetal movements.

AIMS: To enable scientific studies on fetal movements and its relation to fetal heart rate directly detecting fetal chest motion with ultrasonic Doppler method. METHODS: A prototype of an ultrasonic Doppler fetal actocardiograph (ACG) was designed and handmade by the author. A 2 MHz ultrasound fetal heart rate (FHR) monitor was remodeled to detect fetal heartbeat and chest movement Doppler signals with a single ultrasound probe. The fetal movement Doppler signal was 20-50 Hz using 2 MHz ultrasound, separated from the fetal heartbeat Doppler signal, which was 100 or more Hz and sent to the autocorrelation FHR meter to record FHR curve, while fetal movement Doppler signals were detected through 20-80 Hz band-pass filter, and changed to spikes recorded on a cardiotocography chart. RESULTS: The spike amplitudes of a moving steel ball expressed fetal movement on the ACG. FHR acceleration synchronized with fetal movement bursts. Fetal resting and active states are separated using the ACG. Fetal hiccupping movements on ACG were regular continuous spikes with 2-3 s intervals. CONCLUSION: Fetal movements and hiccups were correctly recorded with the FHR curve. The relation of FHR and movement will be further clarified in future ACG readings.

Highly improved perinatal states in Japan.

To report on improved perinatal states in Japan, governmental and United Nations Children's Fund reports were analyzed. Initial maternal mortality, which was 409.8 in 1899, decreased to 4.1 in 2010, with a reduction rate of 409.8/4.1 (102.4) in 111 years: 2.5 in the initial 50 years in home delivery and 39.3 in the later 60 years in hospital births. The difference between 2.5 versus 39.3 was attributed to the medicine and medical care provided in hospital births. The total reduction of neonatal mortality was 77.9/1.1 (70.8), and the rate in the initial 50 versus later 60 years was 2.8/25. Also, there was a big difference after introduction of extensive neonatal care. Virtual perinatal mortality after 22 weeks was estimated to be 428 in 1000 births in 1900 (i.e. those infants born at 22-28 weeks were unlikely to survive at that time), while the perinatal mortality was reported to be 22 weeks or more in 1979 (i.e. premature babies born at ≥22 weeks survived in 1979 because of the improved neonatal care). Actually, 60% of premature infants of 400-500 g survived in the neonatal intensive care unit. In a recent report, 36% of infants born at 22 weeks survived to 3 years. Although there were neurodevelopmental impairments, outcomes were improved. In conclusion, perinatal states have remarkably improved in Japan.

Modalities of fetal evaluation to detect fetal compromise prior to the development of significant neurological damage.

AIMS: The aim of this study was to clarify the developmental mechanism underlying fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect to fetal brain damage. MATERIAL AND METHODS: The fetal state was deduced from the developmental mechanism of FHR variability analyzed by actocardiogram, animal experiments, and simulations. RESULTS: LTV develops due to minor fetal movements in the fetal midbrain, moderate LTV by fetal periodic movements and triangular accelerations by large fetal movement bursts. Stimulation of the fetal midbrain by sound and light produces fetal movements that lead to FHR acceleration. Severe hypoxia can result in the loss of LTV and neuronal necrosis that may damage the fetal brain. Therefore, a cesarean section is recommended prior to the loss of LTV, rather than after its loss. The vagal center of the fetal medulla oblongata is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic rabbits was found to be closely correlated with the PaO2, thus the impact of hypoxia could be estimated by the hypoxia index, which is calculated from the reciprocal of nadir FHR and bradycardia duration. CONCLUSIONS: Analyzing the development of FHR signs could help to diagnose fetal state. An early cesarean section is recommended before the loss of LTV as indicated by the hypoxia index, which will contribute to prevent fetal brain damage and neurological sequels.

Origin of the long-term variability and acceleration of FHR studied for the prevention of cerebral palsy in fetal hypoxia and general insults.

AIMS: The development of fetal heart rate (FHR) variability and acceleration, and their loss in the hypoxic brain damage and cerebral palsy (CP) is investigated. METHODS: FHR, movements in physiologic sinusoidal FHR and fetal movements were studied by actocardiogram. RESULTS: Periodic fetal respiratory movements evoked moderate FHR variation similar to medium variability. Small fetal movements provoked FHR variability, and large fetal movement burst developed the acceleration. The brain centers should be midbrain for variability and acceleration. FHR variability and acceleration develop by the reaction of fetal brain to fetal movements. As severe organic fetal brain damage could develop through fetal hypoxia in the loss of variability, early delivery before the loss of variability will prevent infantile CP. As the abnormal FHR would be developed by fetal brain damage in non-hypoxic fetal insults, early delivery before the loss of variability could also prevent the brain damage in viral and bacterial infections.

Preeclampsia is caused by continuous sympathetic center excitation due to an enlarged pregnant uterus.

AIMS: To deduce the origin of preeclampsia characterized by hypertension and proteinuraia on the basis of results from animal studies and its therapeutic strategies. METHODS: Sympathetic and parasympathetic zones of female non-pregnant rabbit brain were stimulated electrically with Kurotu's electrodes. Systolic blood pressure, urine volume, and proteinuria were evaluated before and after the stimulation of autonomic zones. RESULTS: Excitation, hypertension, urine reduction, cloudy urine, and proteinuria were observed following stimulation of the sympathetic zone. A stable state, low blood pressure, increased urine volume, and no proteinuria were observed following stimulation of the parasympathetic zone. CONCLUSION: Hypertension and proteinuria in preeclampsia are caused by continuous stimulation of the sympathetic nervous center in the hypothalamus through the innervation between the enlarged uterus and hypothalamus in the latter stages of pregnancy or in a complete hydatidiform mole. Future studies are needed to address the potential of pharmacological suppression of an overactive sympathetic nerve system.

A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy.

Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type.

Noninvasive fetal lung maturity prediction based on ultrasonic gray level histogram width.

The aim of this work was to noninvasively predict fetal lung immaturity with the ultrasonic gray level histogram width (GLHW), a form of clinical tissue characterization. The study included 22 fetuses in which infant respiratory distress syndrome (IRDS) developed post-delivery, and 25 fetuses without IRDS development. Independent receiver operating characteristic (ROC) analysis of fetal lung-to-liver GLHW ratios, fetal weights, gestational ages and the product of GLHW ratios by gestational ages for this cohort indicated that optimal thresholds for these parameters to differentiate immature from mature were 0.94, 1.750 g, 31 weeks and 29, respectively. With the optimal decision threshold of 0.94, the GLHW ratio provided sensitivity and specificity of 0.86 and 0.72, respectively. The corresponding values for gestational age were 0.77 and 0.68, 0.77 and 0.60 for fetal weight versus 0.96 and 0.72 for the product of GLHW ratio by fetal age, which was comparable with invasive amniotic fluid tests. The areas under the ROC curve for these parameters were 0.82, 0.82, 0.70 and 0.91. We found that GLHW is a noninvasive, stable and reliable measure of fetal lung maturity using commercial scanners.

Loss of FHR variability diagnosed by frequency analysis.

AIMS: To determine the loss of fetal heart rate (FHR) baseline variability by frequency analysis. METHODS: The FHR tracings of 12 normal fetuses and others with various conditions, as well as flat FHR tracings of a late deceleration (LD) and anencephaly recorded with Doppler fetal monitors, were scanned and processed using fast Fourier transform (FFT) analysis. The ratio of the area under the low frequency spectrum divided by the area under the whole spectrum (La/Ta) and the peak power spectrum density (PPSD) were determined. RESULTS: Long-term variability (LTV) measures >10 bpm revealed significantly more La/Ta and PPSD than LTV <10 bpm in normal FHR tracings. The La/Ta and PPSD were >15% and 60 bpm(2)/Hz, respectively, in representative values of normal FHR cases and in those of fetal respiration, hiccupps and non-reactive FHR, whereas those of the flat baseline of LD and anencephaly were <15% and 60 bpm(2)/Hz. CONCLUSION: Loss of baseline variability is diagnosed when the La/Ta ratio and PPSD are <15% and 60 bpm(2)/Hz, respectively, based on the FFT frequency analysis of the FHR baseline.

Detailed multigrade evaluation of fetal disorders with the quantified actocardiogram.

AIMS: To evaluate fetal disorders using detailed quantitative values from the actocardiogram (ACG) involving simultaneous tracing of ultrasonic Doppler fetal movement bursts and fetal heart rate (FHR). METHODS: Duration of FHR accelerations and fetal movement bursts were measured manually in 20 common fetal disorders. The severity of the fetal disorder was estimated using the FHR acceleration duration to movement burst ratio (A/B ratio) and 10-0 clinical severity ranks derived from the A/B ratio. The correlation of the A/B ratio and 1 and 5 min Apgar scores, as well as numerically expressed long-term outcomes were studied. RESULTS: A/B ratios were significantly correlated with the 1 and 5 min Apgar scores and the numerically evaluated long-term outcomes. Controversial cases of FHR pattern were more easily understood using the A/B ratio. The 10-0 severity derived from the A/B ratio was useful in clinical fetal studies. CONCLUSION: Common fetal disorders were evaluated quantitatively and in more detail using the A/B ratio from the actocardiogram than when using common binary good or bad evaluation. The A/B ratio was useful in outcome estimation, where the prognostic capability of the A/B ratio was confirmed by significant correlation with 1 and 5 min Apgar scores and long-term outcomes of fetal disorders.

Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos.

OBJECTIVE: The purpose of this study was to clarify developmental changes of early human embryos by using time-lapse cinematography (TLC). STUDY DESIGN: For human ova, fertilization and cleavage, development of the blastocyst, and hatching, as well as consequent changes were repeatedly photographed at intervals of 5-6 days by using an inverse microscope under stabilized temperature and pH. Photographs were taken at 30 frames per second and the movies were studied. RESULTS: Cinematography has increased our understanding of the morphologic mechanisms of fertilization, development, and behavior of early human embryos, and has identified the increased risk of monozygotic twin pregnancy based on prolonged incubation in vitro to the blastocyst stage. CONCLUSION: Using TLC, we observed the fertilization of an ovum by a single spermatozoon, followed by early cleavages, formation of the morula, blastocyst hatching, changes in the embryonic plates, and the development of monozygotic twins from the incubated blastocysts.

Fetal extremity kinetics quantified with Doppler ultrasonography.

AIMS: To assess the responsive fetal extremity movement to vibro-acoustic stimulation test (VAST). METHODS: The moving velocity of fetal femur was assessed after VAST by pulsed Doppler device. The ultrasonic beam was insonated at a right angle to the fetal femur. The following parameters were determined: limb retreat velocity in accelerative slope (Pk1); limb replenishment velocity in decelerative slope (Pk2); mean flexion to extension velocity; and the response time to VAST. Among 80 normal singleton pregnancies in 33-41 weeks, 68 were weekly evaluated and the others were assessed for two or more times during the study period, for a total of 680 studies of fetal kinetics. RESULTS: The Pk1 declined from 9.6 to 6.26 cm/s; Pk2 decreased from 2.6 to 1.3 cm/s; mean velocity was reduced from 6.0 to 4.25 cm/s; whereas the response time increased from 0.1 to 0.3 s throughout the study period, i.e., fetal response reduces and the response time increases as maturation progresses. CONCLUSION: The pulsed Doppler may assess fetal activity in any body structure. Reflex responses become slow and complex on both the velocity and response time as maturation increases with gestational age. Our observations have resulted in a novel and easy method for the quantitative assessment of fetal reflex reactivity to external stimuli.