Fetal Biometric Assessment and Infant Developmental Prognosis of the Tadalafil Treatment for Fetal Growth Restriction.

Background and Objectives: Tadalafil is expected to treat fetal growth restriction (FGR), a risk factor for stillbirth and neonatal morbidity. This study aimed to evaluate the fetal biometric growth pattern of fetuses with FGR treated with tadalafil by ultrasonographic assessment. Materials and Methods: This was a retrospective study. Fifty fetuses diagnosed with FGR and treated by maternal administration of tadalafil and ten controls who received conventional treatment at Mie University Hospital from 2015 to 2019 were assessed. Fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) at the start of treatment and at two weeks and four weeks of treatment were mainly assessed by ultrasound examination. The Wilcoxon signed-rank test was used to assess the measures. The Kyoto Scale of Psychological Development (KSPD) was used to assess the developmental prognosis on tadalafil-treated children at 1.5 years of corrected age (CA) and 3 years old. Results: The median gestational age at the start of treatment was 30 and 31 weeks in the tadalafil and control groups, respectively, and the median gestational age at delivery was 37 weeks in both groups. The Z-score of HC was significantly increased at 4 weeks of treatment (p = 0.005), and the umbilical artery resistance index was significantly decreased (p = 0.049), while no significant difference was observed in the control group. The number of cases with an abnormal score of less than 70 on the KSPD test was 19% for P-M, 8% for C-A, 19% for L-S, and 11% for total area at 1.5 years CA. At 3 years old, the respective scores were 16%, 21%, 16%, and 16%. Conclusions: Tadalafil treatment for FGR may maintain fetal HC growth and infants' neuro-developmental prognosis.

Comparison of perinatal outcomes between controlled-release dinoprostone vaginal delivery system (PROPESS) and metreurynter for cervical ripening in labor induction: A retrospective single-center study in Japan.

AIM: This study aimed to compare the efficacy and safety of a controlled-release dinoprostone vaginal delivery system (PROPESS) and a metreurynter for labor induction. METHODS: This retrospective case-controlled study included 117 pregnant women (51 and 66 in the PROPESS and metreurynter groups, respectively) who required labor induction after >37 weeks' gestation at Mie University Hospital between January 2018 and September 2020. The primary outcome was the success rate of vaginal delivery. The secondary outcomes were changes in the Bishop score from the first insertion of PROPESS or the metreurynter to removal, uterine hyperstimulation and non-reassuring fetal status during the first insertion, proportion of pregnant women who needed pre-delivery oxytocin after removal, time to vaginal delivery after the first insertion, proportion of pregnant women who delivered vaginally within 12 or 24 h after the first insertion, and neonatal outcomes. RESULTS: The proportion of pregnant women, especially primiparas, who delivered vaginally was significantly higher in the PROPESS group (26/34 [76.5%]) than in the metreurynter group (25/52 [48.1%]; p = 0.01). Moreover, among multiparas in the PROPESS group who delivered vaginally, nine (56.3%) out of 16 women delivered vaginally within 3 h of labor onset. CONCLUSIONS: PROPESS for cervical ripening may reduce the risk of undergoing cesarean section in pregnant women requiring labor induction, especially primiparas. It is important to consider the possibility of precipitate labor when using the PROPESS in multiparas.

Cytomegalovirus DNA Loads in Organs of Congenitally Infected Fetus.

Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.

A Woman with Rheumatoid Arthritis Who Successfully Delivered a Healthy Child with Continuous Administration of Sarilumab Throughout Pregnancy.

We herein report a patient with rheumatoid arthritis (RA) who successfully delivered a healthy child with continuous administration of sarilumab throughout pregnancy. She delivered her first child, a healthy boy, following in vitro fertilization-embryo transfer (IVF-ET) while using etanercept and low-dose prednisolone. Disease activity persisted after delivery, so etanercept was switched to sarilumab. She became pregnant by IVF-ET again. Because RA was still active, sarilumab was continued during pregnancy. She delivered a healthy girl at the 38th week of gestation by Caesarean section. No abnormalities were detected at or within 6 months after birth. Sarilumab was safe and effective in this pregnant woman with RA.

Revision of Cytomegalovirus Immunoglobulin M Antibody Titer Cutoff in a Maternal Antibody Screening Program in Japan: A Cohort Comparison Involving a Total of 32,000 Pregnant Women.

Cytomegalovirus (CMV) is associated with congenital infections. We aimed to validate the revised CMV immunoglobulin (Ig) M titer cutoff for IgG avidity measurements as a reflex test in maternal screening to identify women with primary CMV infection and newborn congenital cytomegalovirus (cCMV). We screened maternal CMV antibodies (the Denka assay) in Japan, from 2017 to 2019, using a revised IgM cutoff (≥4.00 index). Participants were tested for IgG and IgM antibodies, and for IgG avidity if IgM levels exceeded the cutoff. We compared these with corresponding results from 2013 to 2017 based on the original cutoff (≥1.21) and recalculated using the revised cutoff. Newborn urine CMV DNA tests were performed for women with low avidity (≤35.0%). Among 12,832 women screened in 2017-2019, 127 (1.0%) had IgM above the revised cutoff. Thirty-five exhibited low avidity, and seven infants developed cCMV. Of 19,435 women screened in 2013-2017, 184 (1.0%) had IgM above the revised cutoff, 67 had low avidity, and 1 had cCMV. The 2017-2019 results were not significantly different from the 2013-2017 results. The revised IgM cutoff improves maternal screening in identifying primary infection and newborn cCMV; however, further study related to other assays than Denka is required.

Transient Decrease in Incidence Rate of Maternal Primary Cytomegalovirus Infection during the COVID-19 Pandemic in Japan.

This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015-2019 as the pre-pandemic and 2020-2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level.

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy.

BACKGROUND/AIM: Adverse events associated with long-term bevacizumab administration for ovarian cancer have been poorly documented in Japan. This study aimed to evaluate the adverse events of bevacizumab combined with chemotherapy for treating primary and recurrent epithelial ovarian cancer in Japan. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed data of patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy between January 2013 and November 2019. Statistical analyses were performed using the Fisher's exact test and Kaplan-Meier method. RESULTS: A total of 46 patients were included and the follow-up time was 30 months. The median duration of bevacizumab treatment was 14 months, and the median total dose of bevacizumab was 247.5 mg/kg. The most common adverse events were hypertension (n=30; 65.2%) and proteinuria (n=24; 49%) in all grades. The onset of hypertension and proteinuria occurred at a median of 2 months and 14 months after treatment initiation in all grades, respectively. Gastrointestinal perforation occurred significantly more frequently in patients with a history of radiation therapy. CONCLUSION: This study included cases of primary advanced and recurrent epithelial ovarian cancer, and had a longer observation period and reported more adverse events of bevacizumab with chemotherapy than previous reports. The administration of bevacizumab therapy in patients with a history of radiation should be carefully considered due to increased chances of gastrointestinal perforation.

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan.

OBJECTIVE: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection. MATERIALS AND METHODS: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection. RESULTS: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00-12.00 titers and 100% with 1.21-3.99 IgM titers) (p = 0.048). CONCLUSIONS: Nulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.

Primary cytomegalovirus infection during pregnancy and congenital infection: a population-based, mother-child, prospective cohort study.

OBJECTIVE: This study assessed maternal cytomegalovirus antibodies, and the occurrence of primary and congenital cytomegalovirus infections, and risk factors of congenital infection after a maternal primary infection. STUDY DESIGN: We included 19,435 pregnant women in Japan, who were tested for serum cytomegalovirus antibodies before 20 gestational weeks. Immunoglobulin (Ig) G avidity was evaluated in women with both IgG and IgM antibodies; tests were repeated at ≥28 gestational weeks among women without IgG and IgM antibodies. RESULT: Primary and congenital infections were 162 and 23 cases, respectively. The risk ratios for congenital infection were 8.18 (95% confidence interval: 2.44-27.40) in teenage versus older women, and 2.25 (95% confidence interval: 1.28-3.94) in parity ≥ 2 versus parity ≤ 1. Of 22 live birth congenital infection cases, three had abnormal neurological findings. CONCLUSION: We demonstrated teenage and parity ≥ 2 pregnant women as risk factors of post-primary congenital infection.