Efficacy and safety of controlled-release dinoprostone vaginal delivery system (PROPESS) in Japanese pregnant women requiring cervical ripening: Results from a multicenter, randomized, double-blind, placebo-controlled phase III study.

AIM: To evaluate the efficacy and safety of dinoprostone vaginal insert (PROPESS) in pregnant post-term Japanese women requiring cervical ripening. METHODS: This randomized, double-blind, placebo-controlled study included 114 pregnant Japanese women at term (41 weeks of gestation) requiring cervical ripening (baseline Bishop score (BS) ≤ 4). The primary end-point was the proportion of subjects with successful cervical ripening defined as BS ≥ 7 or vaginal delivery in 12 h. The secondary end-points were changes in BS, proportion of women with vaginal delivery, proportion of women receiving mechanical cervical ripening procedure and use of oxytocic drugs. RESULTS: PROPESS administration for a maximum of 12 h showed significantly higher successful cervical ripening rate (47.4% vs 14.3%, respectively; treatment contrast [TC]: 33.1%; P = 0.0002). The median time from administration to vaginal delivery was significantly shorter in the PROPESS group than in the placebo group (26.18 h vs 33.02 h; OR 2.51; 95% CI [1.60-3.92]; P < 0.0001). In the PROPESS group, the dosage of uterotonic drugs, such as oxytocin, decreased, and the number of patients who used these drugs also decreased. CONCLUSION: PROPESS administration for a maximum of 12 h was an effective and well-tolerated treatment for pregnant Japanese women post-term requiring cervical ripening.

Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

The endocrinological responses of veno-venous extracorporeal membrane oxygenation on hypoxic fetal lambs.

OBJECTIVE: The purpose of this study was to observe endocrinological responses of veno-arterial and veno-venous extracorporeal membrane oxygenation (V-A and V-V ECMO) to support fetal oxygenation in utero. METHODS: An ECMO system with a centrifugal pump was applied to six chronically instrumented fetal lambs, at 126-134 days of gestation. Blood was obtained through a double-lumen catheter inserted into the right atrium. After oxygenation, the blood was returned through a single-lumen catheter into either the carotid artery (veno-arterial; V-A ECMO) or the right atrium (V-V ECMO). After fetal hypoxia had been experimentally produced, V-A ECMO or V-V ECMO was instituted to maintain fetal oxygenation. We compared fetal blood gases and concentrations of atrial natriuretic peptide (ANP), epinephrine and norepinephrine with both routes of ECMO. RESULTS: Fetal carotid artery pH did not change during hypoxemia, but decreased after instituting V-A ECMO and V-V ECMO. After instituting V-A ECMO or V-V ECMO for 30 min, oxygen partial pressure (pO2) in the fetal cranial carotid artery recovered from the hypoxic level. The ANP concentration in V-V ECMO was significantly lower than that in V-A ECMO. Fetal serum epinephrine and norepinephrine concentrations significantly increased in association with hypoxic stimulation. There was a further increase in fetal serum epinephrine concentration after instituting V-A ECMO. No significant difference in concentration was found after instituting V-V ECMO from that of after the institution of V-A ECMO. CONCLUSIONS: This study suggested that V-V ECMO may possibly be less invasive than V-A ECMO for fetal heart, because ANP, a cardiac distress index, was lower in V-V ECMO than in V-A ECMO.

Effects of nitric oxide and prostacyclin on hemodynamic response by big endothelin-1 in near term fetal sheep.

AIMS: To measure plasma concentrations of endothelin (ET)-1, NO metabolites (nitrate/nitrite; NOx) and 6-keto PGF1 alpha (PGF1 alpha) in maternal and fetal sheep blood, and to evaluate the effects of big ET-1 on hemodynamic response, blood gases and NO and 6-keto PGF1 alpha production in near term fetal sheep. METHODS: Hemodynamic parameters were measured during infusion of big ET-1 into the carotid vein in chronically catheterized fetal sheep on day 125 of gestation. Fetal arterial blood samples were obtained for ET-1, PGF1 alpha) and nitrate/nitrite (NOx) measurements. RESULTS: ET-1, NOx and PGF1 alpha plasma concentrations were all significantly higher in fetal compared with the maternal plasma. Big ET-1 significantly decreased fetal systolic and diastolic blood pressure and significantly increased fetal heart rate. Big ET-1 stimulated plasma PGF1 alpha), but not NOx , concentration. CONCLUSIONS: Circulatory regulating factors in the fetus were up-regulated. The effects of ET-1 on fetal hemodynamic response may be mediated via prostacyclin, but not via the NO pathway.

The effect of magnesium sulfate on the behavioral activities of fetal goats.

OBJECTIVES: To investigate fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during administration of magnesium sulfate to fetal goats. METHODS: The fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during 6 hours of continuous magnesium sulfate infusion into the fetal jugular vein were examined in 8 chronically instrumented fetal goats at 124-131 days of gestation. Fetal breathing movements were defined as repetitive negative fluctuations of the fetal tracheal pressure. Fetal electrocortical activities were assessed by visual analysis of periods of high-voltage and low-voltage electrocortical activities. RESULTS: Continuous infusion of magnesium sulfate for 6 hours significantly increased the fetal plasma magnesium concentration from 2.8 +/- 1.2 to 8.3 +/- 2.6 mg/dL without significant changes in fetal arterial blood gases. The incidence of fetal heart rate accelerations during magnesium infusion was significantly decreased from that found during the control periods. After 2 hours of infusion, the incidence of fetal breathing movements significantly decreased from 33.9% +/- 20.5% to 1.2% +/- 1.4% and remained at this level during the remaining 4 hours of magnesium infusion. The percentage of time that the fetuses were found to have low-voltage electrocortical activities decreased from 51.6% +/- 9.0% to 40.4% +/- 8.2% after 2 hours of infusion but recovered to 49.9% +/- 12.0% by 6 hours of magnesium infusion. CONCLUSION: We concluded that fetal magnesium sulfate administration affected fetal heart rate accelerations and fetal breathing movements continuously but electrocortical activities only temporarily during 6 hours of observations.

Fetal hepatic hemangioma representing non-reassuring pattern in fetal heart rate monitoring.

To the best of our knowledge, this is the first report of a non-reassuring fetal pattern caused by a hepatic hemangioma that was found during fetal heart rate monitoring. A 37 weeks' gestation, a 32-year-old-woman was referred to our hospital for evaluation of a rapidly growing fetal abdominal tumor. Fetal heart rate monitoring revealed a non-reassuring pattern, and a cesarean section was performed as a result. Examination of the 2820 g female infant suggested a hepatic hemangioma accompanying an intratumor hemorrhage and coagulopathy. The infant died 2 days after birth. The autopsy confirmed that the cause of death was a result of a hepatic hemangioma. Frequent monitoring of fetuses and ultrasound examinations are necessary for determining the timing of delivery and for a favorable prognosis.