Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor with a long half-life, high selectivity, and rapid onset of action. Because the safety of using PDE5 inhibitors as therapeutic agents for fetal growth restriction (FGR) has been a problem worldwide, this paper primarily focuses on the safety assessments performed in the Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER) II population. Neonatal and maternal adverse events were analyzed, in addition to fetal, neonatal, and infant death cases, six months after stopping the trial. Eighty-nine pregnant women with FGR were studied between September 2016 and March 2018 (45 and 44 in the tadalafil and conventional treatment groups, respectively). Seven (16%) deaths (four fetal, one neonatal, and two infant) in the control group, whereas only one neonatal death occurred in the tadalafil group. Although headache, facial flushing, and nasal hemorrhage occurred more frequently in the tadalafil group, these symptoms were Grade 1 and transient. In conclusion, this trial showed that tadalafil decreased the fetal and infant deaths associated with FGR. This is thought to be primarily due to pregnancy prolongation. Further studies are warranted to evaluate the efficacy of tadalafil in treating early-onset FGR.

Background and Objectives: Tadalafil for treatment of fetal growth restriction (FGR) or preeclampsia is given once a day orally. The drug kinetics of tadalafil were investigated to determine the ideal dosage to promote uterine blood flow. Materials and Methods: We recruited five pregnant women with FGR or preeclampsia before administration of tadalafil, all of which were administered tadalafil (20 mg/day, once-daily dosing). The blood concentration of tadalafil was measured 1, 2, 4, 6, 8, and 24 h after administration, and uterine blood flow was measured before tadalafil administration and 2–4 and 20–24 h after. We then analyzed the correlation between tadalafil blood concentration and uterine artery blood flow. Results: The blood concentration of tadalafil correlated with uterine artery blood flow in pregnant women. The blood concentration of tadalafil and uterine artery blood flow decreased 5 h after administration of tadalafil. Conclusions: The blood concentration of tadalafil and uterine artery blood flow fluctuate in parallel, the latter was decreased by reduced blood concentration. Thus, a study of tadalafil administered twice a day in pregnant women will be needed to stabilize uterine artery blood flow.

Purpose: Hepatitis due to herpes simplex virus (HSV) during pregnancy is rare, it is often not included in the differential disease. However, hepatitis leads to maternal death; hence, early diagnosis is necessary. Hepatic enzyme elevation in late pregnancy is often associated with obstetric-related diseases, such as acute gestational fatty liver and HELLP syndrome (hemolytic anemia, elevated liver enzymes, low platelet count). These pregnancy-related diseases often improve maternal condition after completion of pregnancy, but in patients with HSV hepatitis, invasive treatment, such as cesarean section, may lead to deterioration of maternal condition after completion of pregnancy. A systematic review was conducted to extract necessary factors to avoid maternal death caused by herpetic hepatitis.Methods: In 24 cases reported since 1991, age, onset gestational weeks, initial symptoms, days from onset of symptoms to consultation, diagnosis method, treatment method, maximum liver escape enzyme value during hospitalization, bilirubin value, international normalized ratio value, and fetal/neonatal prognosis were extracted, and the relationship between maternal death group (n = 6) and maternal alive group (n = 18) was statistically analyzed.Results: Fever as an initial symptom was observed in all cases. Maternal death did not occur in patients administered with acyclovir (ACV) as empiric therapy. No difference was found between the two groups in other factors.Conclusion: Early diagnosis and treatment of herpetic hepatitis during pregnancy are important, as well as administration of empiric ACV concurrently with noninvasive diagnosis when a pregnant woman has elevated liver enzyme accompanied by fever in late pregnancy.

Purpose: To investigate the accuracy of computer analysis and its features to be used as a fu fetal heart rate (FHR) interpretation method in clinical settings. Methods: The Trium CTG Online® was used as the computer analysis software. Twenty six cases of intrapartum FHR tracings (total time, 6900 min) were randomly selected from third trimester pregnancies. Three obstetricians blinded to the patients’ clinical information traced the decelerations, variability, and baseline cardiotocogram (CTG) data. Three obstetrician observer individually interpreted the data, and only the waveforms they interpreted were adopted. The agreement between the deceleration and baseline, variability, and level of five-tier system was estimated. Weighted kappa (κ) statistics was used to assess reliability. Results: Based on the observers and Trium’s classification, κ was 0.78 and strength of agreement level was substantial. The obstetricians and Trium mostly agreed on the variability and baseline data. However, κ of each decelerations was approximately 0.65 (0.63–0.66), with substantial strength of agreement. Conclusion: Based on the obstetricians and Trium’s interpretation, the latter was found to be excellent for FHR interpretation. However, it was difficult for Trium to interpret specific waveform patterns. Therefore, clinical staff should understand these characteristics to more sensitively evaluate the fetal well-being.