Shoichi Magawa

Objective: Recurrent fetal heart rate (FHR) decelerations without acidosis are frequently observed during labor; however, the underlying autonomic mechanisms remain incompletely understood. This study explored fetal autonomic responses to recurrent decelerations using FHR and FHR variability (FHRV) parameters. Methods: This retrospective observational study included healthy women with singleton pregnancies, no pregnancy complications requiring treatment, and an umbilical artery pH >7.2 at delivery. Continuous FHR monitoring using fetal head electrodes was performed for ≥2 h before delivery (June–December 2021). FHRV was assessed using time‐domain, frequency‐domain, and nonlinear indices. Results: Twenty‐four patients were included. Baseline FHR did not differ between groups. In the recurrent deceleration group, root mean square of successive differences and high‐frequency power were higher during the final 60 min before delivery. No differences were observed in standard deviation of normal‐to‐normal intervals or very‐low‐frequency power. Sample entropy was also higher, suggesting increased complexity of autonomic regulation. Conclusion: Fetuses with recurrent decelerations without acidosis demonstrated patterns consistent with increased vagal modulation, as inferred from FHRV indices. These findings may reflect an adaptive autonomic response; however, given the exploratory nature and small sample size, further studies are warranted.

Fetal growth restriction (FGR) is a disease during pregnancy that increases the risk of preterm birth and perinatal death. Currently, the diagnosis of FGR relies on ultrasonography-based estimated fetal body weight (EFBW). However, EFBW can only provide an indirect assessment of FGR because a low EFBW is only a result of growth restriction. Recent research has indicated that placental oxygenation function is a key indicator of fetal growth; however, its assessment through ultrasonography is impractical. Techniques other than ultrasonography for placental function have been investigated, and a significant difference in placental oxygenation function between FGR and non-FGR cases has been demonstrated using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). BOLD MRI can visualize oxygenation in vivo, and may be useful as a marker for the direct assessment of placental oxygenation function. However, visual assessment of placental oxygenation in BOLD MRI is challenging, even for experts, because of the complexity of analyzing the signal intensity on MRI. In this study, we proposed an automated method for predicting FGR by utilizing placental image features extracted from BOLD MRI during oxygen administration. In addition to the FGR/non-FGR classification method, we propose a placental region segmentation method to reduce the manual annotation burden. The proposed segmentation method achieved a Dice coefficient of 0.809, outperforming other deep learning methods. In the FGR/non-FGR classification experiments, conducted with four-fold cross-validation on 22 subjects, the highest performance was obtained using a pre-trained ResNet50 combined with a fully connected layer with transfer learning as a feature extractor (subject-wise accuracy of 0.908, ROC-AUC of 0.927, and F1 score of 0.922). These results demonstrate that placental image features extracted from BOLD MRI can effectively differentiate between FGR and non-FGR cases, suggesting the potential for a direct and automated approach to assess FGR through placental oxygenation function.

AimThis study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic-ischemic encephalopathy.MethodsThe study used a three-case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil-associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery.ResultsA total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms-like tyrosine kinase-1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration.ConclusionsThe study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.

COVID-19 is an ongoing pandemic and has been extensively studied. However, the effects of COVID-19 during pregnancy, particularly on placental function, have not been verified. In this study, we used blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate whether COVID-19 incidence during pregnancy has any lasting effects with respect to placental oxygenation. This is a case-control study, in which eight cases of singleton pregnancies before 30 weeks gestation with COVID-19 mothers were included. Placental oxygenation was evaluated using BOLD-MRI after 32 weeks of gestation. BOLD-MRI was consecutively performed under normoxia (21% O₂), hyperoxia (100% O₂), and normoxia for 4 min each. Individual placental time-activity curves were evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). Eighteen COVID-19-free normal pregnancies from a previous study were used as the control group. No significant differences were found between the two groups regarding maternal background, number of days of delivery, birth weight, and placental weight. The parameter peakΔR2* was significantly decreased in the COVID-19 group (8 ± 3 vs. 5 ± 1, p < .001); however, there was no significant difference in time to peakΔR2* (458 ± 74 s vs. 471 ± 33 s, p = .644). In this study, BOLD-MRI was used to evaluate placental oxygenation during pregnancy in COVID-19-affected patients. COVID-19 during pregnancy decreased placental oxygenation even post-illness, but had no effect on fetal growth; further investigation of the possible effects of COVID-19 on the fetus and mother is warranted.

Introduction: With category II fetal heart rate tracings, the preferred timing of interventions to prevent fetal hypoxic brain damage while limiting operative interventions remains unclear. We aimed to estimate fetal extracellular base deficit (BD_ecf) during labor with category II tracings to quantify the timing of potential interventions to prevent severe fetal metabolic acidemia.Material and methods: A longitudinal study was conducted using the database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, including infants with severe cerebral palsy born at ≥34 weeks' gestation between 2009 and 2014. Cases included those presumed to have an intrapartum onset of hypoxic–ischemic insult based on the fetal heart rate pattern evolution from reassuring to an abnormal pattern during delivery, in association with category II tracings marked by recurrent decelerations and an umbilical arterial BD_ecf ≥ 12 mEq/L. BD_ecf changes during labor were estimated based on stages of labor and the frequency/severity of fetal heart rate decelerations using the algorithm of Ross and Gala. The times from the onset of recurrent decelerations to BD_ecf 8 and 12 mEq/L (Decels‐to‐BD8, Decels‐to‐BD12) and to delivery were determined. Cases were divided into two groups (rapid and slow progression) based upon the rate of progression of acidosis from onset of decelerations to BD_ecf 12 mEq/L, determined by a finite‐mixture model.Results: The median Decels‐to‐BD8 (28 vs. 144 min, p < 0.01) and Decels‐to‐BD12 (46 vs. 177 min, p < 0.01) times were significantly shorter in the rapid vs slow progression. In rapid progression cases, physicians' decisions to deliver the fetus occurred at ~BD_ecf 8 mEq/L, whereas the “decisions” did not occur until BD_ecf reached 12 mEq/L in slow progression cases.Conclusions: Fetal BD_ecf reached 12 mEq/L within 1 h of recurrent fetal heart rate decelerations in the rapid progression group and within 3 h in the slow progression group. These findings suggest that cases with category II tracings marked by recurrent decelerations (i.e., slow progression) may benefit from operative intervention if persisting for longer than 2 h. In contrast, cases with sudden bradycardia (i.e., rapid progression) represent a challenge to prevent severe acidosis and hypoxic brain injury due to the limited time opportunity for emergent delivery.

The association between prepartum time-series fetal heart rate pattern changes and cord blood gas data at delivery was examined using the conventional 5-tier classification and the Rainbow system for 229 female patients who delivered vaginally. They were classified into three groups based on the results of umbilical cord blood gas analysis at delivery. The fetal heart rate pattern classifications were based on analysis of measurement taken at 10-min intervals, beginning at 120 min pre-delivery. The relationship between fetal heart rate pattern classification and cord blood pH at delivery changed over time. The 5-tier classification at each interval increased before delivery in the Mild and Severe groups compared with the Normal group. No significant differences were observed between acidemia groups. The Rainbow classification showed a significant differences between the acidemia groups at each interval, particularly during the prepartum period. A relationship between classification and outcome was evident before delivery for both the 5-tier classification and Rainbow system.