Modes of delivery and indications in women with COVID-19: a regional observational study in Japan.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, caesarean section (CS) has been the preferred deliver method for pregnant women with COVID-19 in order to limit the use of hospital beds and prevent morbidity among healthcare workers. METHODS: To evaluate delivery methods used during the COVID-19 pandemic as well as the rates of adverse events and healthcare worker morbidity associated with caesarean deliveries. METHODS: We investigated maternal and neonatal backgrounds, delivery methods, indications and complication rates among pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture, Japan. The predominant mutation period was classified as the pre-Delta, Delta and Omicron epoch. RESULTS: Of the 1291 pregnant women with COVID-19, 59 delivered; 23 had a vaginal delivery and 36 underwent CS. Thirteen underwent CS with no medical indications other than mild COVID-19, all during the Omicron epoch. Neonatal complications occurred significantly more often in CS than in vaginal delivery. COVID-19 in healthcare workers was not attributable to the delivery process. CONCLUSION: The number of CS with no medical indications and neonatal complications related to CS increased during the COVID-19 pandemic. Although this study included centres that performed vaginal deliveries during COVID-19, there were no cases of COVID-19 in healthcare workers. It is possible that the number of CS and neonatal complications could have been reduced by establishing a system for vaginal delivery in pregnant women with recent-onset COVID-19, given that there were no cases of COVID-19 among the healthcare workers included in the study.

We evaluated the incidence of adverse events associated with caesarean section (CS) deliveries and the morbidity of health care workers, which increased during the coronavirus infection pandemic. Maternal and neonatal background, delivery methods, indications and complication rates of pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture were investigated by time of onset. Of the 1291 pregnant women with COVID-19, 59 delivered while affected; 23 underwent vaginal delivery and 36 CS. Of these, 13 who underwent CS in the omicron epoch had no medical indication other than mild COVID-19. Neonatal complications were significantly more common with CS than with vaginal delivery, and there was no occurrence of COVID-19 in healthcare workers. In this study, there were no cases of COVID-19 among health care workers; establishing a system to perform vaginal delivery for pregnant women with COVID-19 could have reduced the number of CS and neonatal complications.

A Novel Method for Determining Fibrin/Fibrinogen Degradation Products and Fibrinogen Threshold Criteria via Artificial Intelligence in Massive Hemorrhage during Delivery with Hematuria.

(1) Background: Although the diagnostic criteria for massive hemorrhage with organ dysfunction, such as disseminated intravascular coagulation associated with delivery, have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with >2000 mL of blood loss, among 13,368 deliveries, was obtained from nine national perinatal centers in Japan between 2020 and 2023. Twenty-three patients had fibrinogen levels <170 mg/dL, which is the initiation of coagulation system failure, according to our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. A positive FDP-fibrinogen/3-60 (mg/dL) value indicates hematuria; otherwise, the case is nonhematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: Using artificial intelligence, the borderline criterion was obtained, which divides the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery; this method appears to be useful.

Comparative study of the usefulness of risk score assessment in the early stages of COVID-19 affected pregnancies: Omicron variant versus previous variants.

AIM: To evaluate the utility of the risk score in assessing the current status and prognosis of COVID-19 in pregnancy. METHODS: Seventy-seven cases affected before the Omicron variant epidemic and 50 pregnant cases affected by the Omicron variant were included. The risk score consists of maternal background, current condition, and examination findings. We determined the risk score in the early stages of disease onset. RESULTS: There were no significant differences in the maternal or gestational ages between the groups. The risk score was significantly lower in the After-Group patients (those affected during the Omicron epoch), while 14.3% of the Before-Group patients (those affected during the pre-Delta and Delta epochs), experienced a worsening of disease after the visit to the center, whereas none of the After-Group patients did. The Before Group's frequency of risk score items was higher among the two groups for "fever for ≥48 h," "mild pneumonia image," and "blood tests," whereas "disease onset 14 days after the second vaccination" was increased in After Group. The blood test parameters for platelet count, C-reactive protein, and D-dimer levels were not significantly different between the groups. CONCLUSIONS: The risk score system appeared superior in detecting deteriorating cases. There were no cases of post-illness deterioration in the After-Group, suggesting that cases of the Omicron variant in pregnancy may have had a less severe course compared to that of previous variants. However, there was no significant difference between the groups in terms of a specific blood test evaluation, suggesting the need for a combined evaluation of cases affected during pregnancy.

Evaluation of the tolerability of monoclonal antibody therapy for pregnant patients with COVID-19.

AIM: To evaluate the tolerability of casirivimab and imdevimab (CAS/IMB) therapy in pregnant women with COVID-19 in Japan and its impact on the neonate and process of delivery. METHODS: Eight cases of pregnancy complicated by COVID-19 and requiring hospitalization during the delta variant epidemic were included. Gestational age, initial symptoms, pregnancy complications and outcome, severity of illness, blood test findings at the time of treatment initiation and on days 3-5 after administration, body temperature at administration, and 8, 24, and 48 h post-administration, delivery outcome, and neonatal findings were recorded. Ten pregnant women who required hospitalization at the same time and did not receive CAS/IMB were used as controls. RESULTS: Of the eight cases, seven were mild, and one case was of moderate severity. Body temperature in the CAS/IMB group was significantly higher at 8 h post-administration than that at the time of administration. However, body temperature significantly reduced at 24 and 48 h post-administration in the CAS/IMB group compared with that in the control group. There were no apparent adverse events after CAS/IMB administration. CONCLUSIONS: Maternal administration of CAS/IMB was safe. Although it was difficult to evaluate the improvement in disease by blood test findings, the fever improved within 24 h, which suggests rapid improvement in patient condition.

Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb).

INTRODUCTION: TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial. METHODS AND ANALYSIS: This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication. ETHICS AND DISSEMINATION: This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications. TRIAL REGISTRATION: jRCTs041190065.

Intrauterine fetal death during COVID-19 pregnancy: Typical fetal heart rate changes, coagulopathy, and placentitis.

Although various perinatal outcomes in coronavirus disease 2019 (COVID-19) pregnancies have been reported, the fetal and neonatal consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unclear. Several reports of miscarriages and stillbirths have been recorded, but vertical transmission by SARS-CoV-2 is considered very rare, and the cause remains unknown. We report a case of a 22-year-old uncomplicated Japanese woman infected with SARS-CoV-2 during the second trimester, resulting in intrauterine fetal death due to placental insufficiency associated with COVID-19 placentitis. This report emphasizes the importance of longitudinal assessment of fetal well-being by fetal heart rate monitoring and early detection of maternal coagulation dysfunction representing SARS-CoV-2 inflammation to manage COVID-19 in pregnancy.

Evaluation of Maternal and Neonatal Outcomes of Assisted Reproduction Technology: A Retrospective Cohort Study.

BACKGROUND: To evaluate maternal and neonatal outcomes of assisted reproductive technology (ART). MATERIALS AND METHODS: Pregnant women registered from 2015 through 2017 (n = 6994) at five perinatal centers that managed high-risk pregnancies in Mie, Japan, retrospectively. Rates of preterm birth (<37 gestational weeks), early onset preeclampsia (<34 gestational weeks), late onset preeclampsia (≥34 gestational weeks), low-lying placenta, placenta previa, placenta accreta, placental abruption, atonic bleeding, uterine rupture, and amniotic fluid embolism after ART were evaluated. ART was defined as in vitro fertilization and micro-fertilization. Fisher's exact test, Mann-Whitney's U test, and logistic regression analysis were used to analyze the data. RESULTS: Rates of obstetrical complications including low-lying placenta, placenta previa, placenta accreta, and atonic bleeding were increased with ART compared to those with the control. Particularly, ART was associated with a significantly increased rate of placenta accreta (adjusted odds ratio: 7.35, 95% confidence interval (CI): 3.20-16.6) and significantly decreased rate of placental abruption (adjusted odds ratio: 0.24, 95% CI: 0.07-0.61). CONCLUSIONS: This study showed that ART may reduce placental abruption and increase placenta previa. There is a possibility that the placenta attaches deeper in the myometrium because of ART.

Molecular-targeted therapy for advanced anaplastic thyroid cancer combined with nutritional support.

Management of anaplastic thyroid cancer (ATC) is often difficult because of its aggressive characteristics. Molecular-targeted therapy was recently introduced as an alternative therapeutic strategy for ATC; lenvatinib is a molecular-targeted agent that is currently indicated only in Japan for the treatment of ATC. Here we report the case of an 86-year-old Japanese woman with ATC who was treated with lenvatinib at our hospital and exhibited a remarkable response. Computed tomography showed tumor shrinkage by day 8 and stable disease until day 32. She maintained activities of daily living (ADLs) until shortly before her death. The patient's resting energy expenditure and body composition were analyzed at the time of admission. Potential toxicity risk of lenvatinib was evaluated based on these data. Enteral nutrition for oral intake was supplied to compensate for her lack of dietary intake and to improve metabolism for the purpose of suppressing lenvatinib toxicity. She also engaged in physical rehabilitation to avoid developing sarcopenia, which is thought to be a risk factor of molecular-targeted therapy toxicity, and to maintain her activity level. We emphasize the importance of a team approach for providing an appropriate treatment regimen to maintain ADLs, which includes nutritional support, physical rehabilitation, and aggressive therapy with lenvatinib.

Identification of free radical species derived from caffeic acid and related polyphenols.

Polyphenols are widely distributed in various fruits, vegetables and seasonings. It is well known that they have several physiological effects due to their antioxidative activities. Their activities depend on structural characteristics that favour the formation of their corresponding stable radicals. During the examination at which pH values, the polyphenol radicals are stabilized, we confirmed that polyphenol radicals were stabilized in NaHCO3/Na2CO3 buffer (pH 10) rather than in physiological pH region. Then, we measured electron spin resonance (ESR) spectra at pH 10 to examine the characteristics of free radical species derived from caffeic acid (CA) with an unsaturated side chain, dihydrocaffeic acid (DCA) with a saturated side chain, chlorogenic acid (ChA) and rosmarinic acid (RA). In analyzing the radical structures, ESR simulation, determinations of macroscopic and microscopic acid dissociation constants and molecular orbital (MO) calculation were performed. In CA, the monophenolate forms were assumed to participate in the formation of free radical species, while in DCA, the diphenol form and the monophenolate forms were presumed to contribute to the formation of free radical species. On the basis of the results, we propose the possible structures of the free radical species formed from polyphenols under alkaline conditions.

Screening tests for gestational diabetes in Japan in the 1st and 2nd trimester of pregnancy.

The objective of this study was to investigate the utility and characteristics of various screening procedures for gestational diabetes mellitus (GDM) in Japan during the first trimester and between 24 and 28 weeks of pregnancy. The subjects were 749 pregnant women who came to our hospitals. A 50-g oral glucose challenge test (GCT), casual plasma glucose measurements, fasting blood glucose measurements, and glycosylated hemoglobin measurements were performed in the first trimester. Subjects with no abnormalities were tested again at 24-28 weeks of gestation. Of the 749 subjects, 22 (2.9%) tested positive for GDM. Of those 22 patients, 14 were diagnosed with GDM in the first trimester (63.6%) and eight in the second trimester (36.4%). This finding suggests the importance of screening for glucose intolerance in the first trimester. Furthermore, it appears that the GCT has the most utility for GDM screening; the other screening methods tested were not as useful because of their low sensitivity, particularly in the second trimester.