Breast milk concentrations of acetaminophen and diclofenac - unexpectedly high mammary transfer of the general-purpose drug acetaminophen.

BACKGROUND: Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques. METHODS: We conducted a study on 20 postpartum mothers from August 2019-March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach. RESULTS: For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093. CONCLUSIONS: While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.

Investigation of optimal weight gain during pregnancy: A retrospective analysis of the Japanese perinatal registry database.

AIM: This study aimed to determine the weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy body mass index (BMI) and make recommendations for optimal weight gain in Japan. METHODS: The Japan Society of Obstetrics and Gynecology perinatal database for 2015-2017 was used. From the 719 723 deliveries included in this database, parturients with underlying diseases or missing data were excluded, and 419 114 deliveries were analyzed. A questionnaire survey was also conducted to weigh each perinatal adverse event. For each of the nine outcomes, a restricted cubic spline model was made to estimate the association between the "expected gestational weight gain at 40 weeks" and the outcome risk. RESULTS: Since the classes of medical facilities were generally the same, weights were assigned according to the mean of the questionnaires rather than by the class of the facility. For each pre-pregnancy BMI, the weight gains during pregnancy that minimized the predicted probability of various adverse perinatal events were 12-15, 10-13, 7-10, and upper limit of 5 kg for the underweight, normal-weight, obese 1, and obese ≥2 groups, respectively. CONCLUSIONS: The weight gain during pregnancy that minimizes the predicted probability of various perinatal adverse events according to the pre-pregnancy BMI was established.

Effects of valproic acid on syncytialization in human placental trophoblast cell lines.

The placenta is a critical organ for fetal development and a healthy pregnancy, and has multifaceted functions (e.g., substance exchange and hormone secretion). Syncytialization of trophoblasts is important for maintaining placental functions. Epilepsy is one of the most common neurological conditions worldwide. Therefore, this study aimed to reveal the influence of antiepileptic drugs, including valproic acid (VPA), carbamazepine, lamotrigine, gabapentin, levetiracetam, topiramate, lacosamide, and clobazam, at clinically relevant concentrations on syncytialization using in vitro models of trophoblasts. To induce differentiation into syncytiotrophoblast-like cells, BeWo cells were treated with forskolin. Exposure to VPA was found to dose-dependently influence syncytialization-associated genes (ERVW-1, ERVFRD-1, GJA1, CGB, CSH, SLC1A5, and ABCC4) in differentiated BeWo cells. Herein, the biomarkers between differentiated BeWo cells and the human trophoblast stem model (TSCT) were compared. In particular, MFSD2A levels were low in BeWo cells but abundant in TSCT cells. VPA exposure affected the expression of ERVW-1, ERVFRD-1, GJA1, CSH, MFSD2A, and ABCC4 in differentiated cells (ST-TSCT). Furthermore, VPA exposure attenuated BeWo and TSCT cell fusion. Finally, the relationships between neonatal/placental parameters and the expression of syncytialization markers in human term placentas were analyzed. MFSD2A expression was positively correlated with neonatal body weight, head circumference, chest circumference, and placental weight. Our findings have important implications for better understanding the mechanisms of toxicity of antiepileptic drugs and predicting the risks to placental and fetal development.

Relationship between out-of-facility deliveries and distance and travel time to delivery facilities in Hokkaido, Japan: An ecological study.

AIM: This study aimed to investigate the relationship between the distance and travel time from each municipality to the nearest delivery facilities in the other municipalities and the frequency of out-of-facility deliveries in Hokkaido. METHODS: Vital statistics from 2016 to 2020 were used. For municipalities without delivery facilities, the distance and travel time from the town office of each municipality to the nearest delivery facility was measured using Google maps. Negative binomial regression with an offset term was used to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of out-of-facility delivery for distance (<30, 30-59, ≥60 km), and travel time by car (<30, 30-59, and ≥60 min) from the town office to the nearest delivery facility compared with the presence of delivery facilities. RESULTS: The overall rate of out-of-facility deliveries in Hokkaido was 2.1‰; in municipalities with delivery facilities, 1.8‰, and in municipalities without delivery facilities, 3.1‰. The adjusted RRs (95% CIs) for out-of-facility deliveries were significantly higher in municipalities with less than 30 km and travel time of less than 30 min to delivery facilities, 2.63 (1.34-5.17) and 2.76 (1.36-5.58), respectively, compared to municipalities with delivery facilities. However, the adjusted RR of out-of-facility delivery for municipalities ≥30 km was higher, although the difference was not significant. CONCLUSIONS: Even in municipalities with a distance to delivery facilities of less than 30 km or travel time of less than 30 min, we should keep in mind the occurrence of out-of-facility deliveries.

Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism.

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased NOD.H2b compared to healthy BALBc mice and Thrombospondin-1-null (TSP-1-/-) compared to TSP-1WTC57BL/6J mice. Inflammasome activation was investigated by immunostaining using the R26ASC-citrine reporter mouse, by Western blotting, and by RNAseq. LPS/Nigericin, IL-1α and chronic inflammation induced inflammasomes in lacrimal gland epithelial cells. Acute and chronic inflammation of the lacrimal gland upregulated multiple inflammasome sensors, caspases 1/4, and interleukins Il1b and Il18. We also found increased IL-1ß maturation in Sjögren's syndrome models compared with healthy control lacrimal glands. Using RNA-seq data of regenerating lacrimal glands, we found that lipogenic genes were upregulated during the resolution of inflammation following acute injury. In chronically inflamed NOD.H2b lacrimal glands, an altered lipid metabolism was associated with disease progression: genes for cholesterol metabolism were upregulated, while genes involved in mitochondrial metabolism and fatty acid synthesis were downregulated, including peroxisome proliferator-activated receptor alpha (PPARα)/sterol regulatory element-binding 1 (SREBP-1)-dependent signaling. We conclude that epithelial cells can promote immune responses by forming inflammasomes, and that sustained inflammasome activation, together with an altered lipid metabolism, are key players of Sjögren's syndrome-like pathogenesis in the NOD.H2b mouse lacrimal gland by promoting epithelial dysfunction and inflammation.

C-reactive protein level predicts need for medical intervention in pregnant women with SARS-CoV2 infection: A retrospective study.

AIM: To make effective use of the limited available hospital space during the Coronavirus disease 2019 (COVID-19) pandemic, we conducted this study to investigate the laboratory indices that identify pregnant women with SARS-CoV2 infection who require medical intervention. METHODS: We carried out a retrospective analysis of pregnant women positive for COVID-19 who were admitted to Hokkaido University Hospital from September 2020 to June 2021. Medical interventions included oxygen supplementation, systemic corticosteroids, or supplemental liquids to treat infection-related symptoms. RESULTS: Forty-two infected pregnant patients were admitted to the hospital, half of whom required medical intervention (n = 21). Fever, C-reactive protein (CRP), and platelet count are all associated with need for medical intervention. Of the 32 patients with a fever of ≥37.5°C on days 0-3 after onset of syndromes, 22 (69%) continued to have a fever on days 4-6, of which 19 (86.4%) required medical intervention. CRP level on days 4-6 predicted the presence or absence of medical intervention (area under the receiver operating characteristic curve = 0.913), with a sensitivity of 81% and specificity of 100% at a CRP cutoff of 1.28 mg/dL. CONCLUSIONS: The need for medical intervention in pregnant patients can be predicted with high accuracy using a CRP cutoff of 1.28 mg/dL on days 4-6 after onset of syndromes. The presence of fever also may be an easy marker for selecting subjects who need or will need therapeutic intervention. These could be an effective triage method to determine appropriate indications for the hospitalization of pregnant women in future outbreaks.

Challenges facing workstyle reform for Japanese obstetricians and gynecologists revealed from time studies.

AIM: We aimed to grasp the actual working hours of Japanese obstetricians and gynecologists (OB/GYN doctors) as accurately as possible, using the same method of the Ministry of Health, Labour, and Welfare (MHLW). METHODS: The time study targeted OB/GYN doctors working at 10 universities nationwide including Niigata University and 21 institutions which take a role of perinatal care in Niigata prefecture. Working hours per week were calculated based on the following categories: regular and overtime work inside the hospital, work outside the hospital, self-improvement, education, research, and others. Data on weekly working hours were converted to yearly data for analyses. RESULTS: A time study of 10 universities nationwide revealed that 30% of doctors work overtime for more than 1860 h even if they do not include on-call shifts in their working hours. In 21 institutions in Niigata, physicians in Niigata University worked more overtime than other hospitals. It became clear that community health care was supported by dispatching physicians working at university. Furthermore, the results of simulations predicted the pessimistic situation of perinatal medical care in Niigata. CONCLUSIONS: Our study showed the possibility to exist much more OB/GYN doctors who work more than 1860 h of overtime work per year than the data presented by the MHLW based on nation-wide survey in 2019. The fact that the working hours at the side jobs had a great influence on the increase in overtime work of physicians in University was the same result as the report of MHLW published in 2021.

Mild thrombocytopenia indicating maternal organ damage in pre-eclampsia: a cross-sectional study.

BACKGROUND: Currently, there is a disagreement between guidelines regarding platelet count cut-off values as a sign of maternal organ damage in pre-eclampsia; the American College of Obstetricians and Gynecologists guidelines state a cut-off value of < 100 × 109/L; however, the International Society for the Study of Hypertension in Pregnancy guidelines specify a cut-off of < 150 × 109/L. We evaluated the effect of mild thrombocytopenia: platelet count < 150 × 109/L and ≥ 100 × 109/L on clinical features of pre-eclampsia to examine whether mild thrombocytopenia reflects maternal organ damage in pre-eclampsia. METHODS: A total of 264 women were enrolled in this study. Participants were divided into three groups based on platelet count levels at delivery: normal, ≥ 150 × 109/L; mild thrombocytopenia, < 150 × 109/L and ≥ 100 × 109/L; and severe thrombocytopenia, < 100 × 109/L. Risk of severe hypertension, utero-placental dysfunction, maternal organ damage, preterm delivery, and neonatal intensive care unit admission were analyzed based on platelet count levels. Estimated relative risk was calculated with a Poisson regression analysis with a robust error. RESULTS: Platelet counts indicated normal levels in 189 patients, mild thrombocytopenia in 51 patients, and severe thrombocytopenia in 24 patients. The estimated relative risks of severe thrombocytopenia were 4.46 [95 % confidence interval, 2.59-7.68] for maternal organ damage except for thrombocytopenia, 1.61 [1.06-2.45] for preterm delivery < 34 gestational weeks, and 1.35 [1.06-1.73] for neonatal intensive care unit admission. On the other hand, the estimated relative risks of mild thrombocytopenia were 0.97 [0.41-2.26] for maternal organ damage except for thrombocytopenia, 0.91 [0.62-1.35] for preterm delivery < 34 gestational weeks, and 0.97 [0.76-1.24] for neonatal intensive care unit admission. CONCLUSIONS: Mild thrombocytopenia was not associated with severe features of pre-eclampsia and would not be suitable as a sign of maternal organ damage.

Predictors of recurrent gestational diabetes mellitus: A Japanese multicenter cohort study and literature review.

AIM: To clarify whether maternal characteristics or laboratory parameters could help predict the onset of recurrent gestational diabetes mellitus (GDM). METHODS: We enrolled 615 women with consecutive singleton deliveries at or after 28 GW from two perinatal medical centers between 2011 and 2019 and divided them into four groups according to whether they had GDM in the first and second pregnancies. The outcome of this study was to clarify the incidence and the predictors of recurrent GDM. RESULTS: We found that among 72 women (11.7%) who had GDM during their first pregnancy, the rate of recurrent GDM was 47.2%. The 34 women (5.5%) with recurrent GDM gained significantly less weight in the first and second pregnancies and lost less weight between the first delivery and the second conception compared with those women without GDM in both pregnancies. Of women with GDM during the first pregnancy, 21 scored 2 or 3 (multiple) positive points on a 75-g oral glucose tolerance test (OGTT) during their first pregnancies; the GDM recurrence rate among these women (66.7%) was significantly higher than that among the 51 women who scored 1 positive point (39.2%; p = 0.0411). During the first pregnancy, insulin administration therapy was significantly more frequent in women with recurrent GDM than in women without recurrent GDM (23.5% vs. 5.3%, p = 0.0396, respectively). CONCLUSION: A predictor of recurrent GDM onset was a score of 2 or 3 positive points on the OGTT during the first pregnancy.

The physical and mental burden on obstetricians and gynecologists during the COVID-19 pandemic: A September 2020 questionnaire study.

AIM: The aim of this study was to clarify the physical and mental burden of the COIVD-19 pandemic on obstetricians and gynecologists in Japan and to identify factors that increase the burden of their psychological stress. METHODS: A web-based questionnaire was sent to obstetricians and gynecologists in Japan via email and social media to collect voluntary responses. This survey was conducted from September 1 to 30, 2020. RESULTS: A total of 852 valid responses were included in the analysis; 76% (644) of the physicians felt that the COVID-19 pandemic caused them physical and mental stress equal to or greater than the most severe disaster they had ever experienced. Physicians who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients (odds ratio (OR) 1.571, p = 0.012). Physicians experienced great stress to the point of wearing heavy personal protective equipment during routine vaginal deliveries by mothers with no COVID-19 symptoms. This trend was markedly pronounced for physicians working in regions with fewer cases of COVID-19 infection. CONCLUSIONS: Obstetricians and gynecologists who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients. One potential reason for this may be that they were required to wear more personal protective equipment than necessary. Infection control methods that ensure the safety of obstetricians and gynecologists while not causing unnecessary physical or psychological stress are needed.

Excessive gestational weight gain during the week prior to delivery as a predictor of maternal life-threatening complications in preeclamptic women.

AIM: To investigate the relationship between excessive gestational weight gain during the week prior to delivery (GWG) and severe morbidity and pregnancy termination among pregnant women with preeclampsia (hypertension with proteinuria). METHODS: We compared GWG, laboratory data, and complication(s) between 94 preeclamptic women (preeclampsia group) with singleton pregnancies who delivered at ≥22 gestational weeks and 188 healthy women (control group) with singleton pregnancies undergoing elective cesarean deliveries. The gestational weeks at delivery were matched in the preeclampsia and control groups. RESULTS: Among 282 total participants, median of GWG was significantly higher in the preeclampsia group than in the control group (1.6 kg vs. 0.5 kg, p < 0.0001). Furthermore, the GWG cutoff value for the preeclampsia group was 1.6 kg. The odds ratio for morbidity of preeclampsia among the women with GWG ≥1.6 kg at delivery was 12.5 (95% confidence interval, 6.31-24.5). In the preeclampsia group, 47 women with GWG ≥1.6 kg had significantly higher risks of hypoproteinemia, proteinuria, and renal dysfunction than those of 47 women with GWG < 1.6 kg. While, multivariate analysis showed 1.5 kg was a GWG cutoff value for predicting maternal morbidity (p < 0.0001); preeclamptic women with GWG ≥1.5 kg had a significantly higher risk of pulmonary edema than preeclamptic women with GWG < 1.5 kg (odds ratio, 7.77; 95% confidence interval, 1.64-36.7). CONCLUSION: Excessive GWG in women with preeclampsia might be a predictor for severe maternal life-threatening complications requiring pregnancy termination.

Spontaneous labor curve based on a retrospective multi-center study in Japan.

AIM: In Japan, the criteria of the latent and active phases of the first stage of labor have not been decided. The Japan Society of Obstetrics and Gynecology (JSOG) Perinatal Committee conducted a study to construct a spontaneous labor curve in order to determine the point of onset of the active phase. METHODS: The participants were women who had spontaneous deliveries at four health facilities in Japan between September 1, 2011, and September 31, 2019. Spontaneous delivery was defined as the spontaneous onset of labor at term (37 weeks, 0 days to 41 weeks, 6 days) with vaginal delivery of a mature fetus in a cephalic position without uterotonic agents or epidural analgesia. The time points for each "cm" of dilation were collected starting from the time of full dilation retrogradely. The relationship between time since labor onset and cervical dilation was expressed as a curve using a smoothing B-spline. RESULTS: A total of 4215 primiparous and 5266 multiparous women were included in this study. The spontaneous labor curve showed that in both primiparous and multiparous women, labor progress was slow until 5 cm cervical dilation, accelerating between 5 and 6 cm dilation, and steadily progressed after 6 cm dilation. CONCLUSION: We propose that the active phase of the first stage of labor be defined as starting at 5 cm dilation of the cervix, and that it be divided into an acceleration phase (5-6 cm dilation) and a maximal phase (>6 cm dilation).

Survey of attitudes of individuals who underwent remote prenatal check-ups and consultations in response to the COVID-19 pandemic.

AIM: Perinatal telemedicine efforts have commenced worldwide in response to the COVID-19 pandemic. As there have been no prior studies on the acceptance of telemedicine by pregnant women, we conducted this survey to investigate the same. METHODS: We conducted an anonymous questionnaire survey of pregnant women who underwent telemedicine check-ups from March 4 to June 30, 2020, using a mobile fetal heart rate monitor and video call system through the Hokkaido University Hospital. RESULTS: Out of the 77 individuals who received prenatal telemedicine check-ups, 54 individuals (70%) had complications, and 64 individuals (83%) consented for the questionnaire survey. In the video call system, 18 individuals (28%) were found to be unwell and 17 individuals (27%) experienced difficulty using the mobile fetal heart rate monitoring device. Assuming scores for face-to-face consultations were five out of 10, the mean score for satisfaction was 4.2, but 19 (30%) women felt equal or greater satisfaction with face-to-face consultations. If not for the threat of COVID-19, only four individuals (6%) proactively expressed a desire for telemedicine, with a significantly less demand observed among primiparous women than multiparous women. The permissible additional financial burden enabling telemedicine was $10 or less for 80% of subjects. CONCLUSION: In this small preliminary study, 30% of the pregnant women felt equal or greater satisfaction with telemedicine than face-to-face consultations. A stronger demand for telemedicine was exhibited by multiparous women than primiparous women. Thus, a system that would be advantages by limiting subjects and enabling low-cost examinations is required for making perinatal telemedicine more popular.

Psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 pandemic.

AIM: To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this cross-sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi-squared test. The relationship between COVID-19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model. RESULTS: Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205-1.753; K6: aOR 1.601, 95% CI 1.338-1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066-1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296-2.133) and puerperal women (aOR 1.604, 95% CI 1.006-2.557). CONCLUSIONS: Decreased support due to the COVID-19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.

Attitudes toward overtime work and self-training: A survey on obstetricians and gynecologists in Japan.

AIM: The Ministry of Health, Labour, and Welfare of Japan proposed a regulation of overtime work as a reform in work style. However, the regulation may deteriorate the quality of medical services due to the reduction in training time. Thus, the study aimed to reveal perceptions in terms of generation gaps in views on self-training and overtime work, among members of the Japan Society of Obstetrics and Gynecology (JSOG). METHODS: A web-based, self-administered questionnaire survey was conducted among members of the JSOG. In total, 1256 respondents were included in the analysis. Data were collected on age, sex, experience as a medical doctor, location of workplace, work style, the type of main workplace, and number of full-time doctors in the main workplace. The study examined the attitudes of the respondents toward overtime work and self-training. The respondents were categorized based on experience as a medical doctor. RESULTS: According to years of experience, 112 (8.9%), 226 (18.0%), 383 (30.5%), 535 (42.6%) doctors have been working for ≤5, 6-10, 11-19, and ≥ 20 years, respectively. Although 54.5% of doctors with ≤5 years of experience expected the regulation on working hours to improve the quality of medical services, those with ≥20 years of experience expressed potential deterioration. After adjusting for covariates, more years of experience were significantly related with the expectation of deterioration in the quality of medical services. CONCLUSIONS: The study revealed a generation gap in the views about self-training and overtime work among obstetricians and gynecologists in Japan.

Tailored radical hysterectomy for locally advanced cervical cancer.

OBJECTIVE: The survival and prognostic factors for locally advanced cervical cancer treated with nerve-sparing Okabayashi-Kobayashi radical hysterectomy have not been elucidated. We aimed to evaluate the oncological outcomes of those patients after radical hysterectomy with adjuvant chemotherapy. METHODS: This retrospective cohort study was conducted from January 2002 to December 2011. Treatment was conducted at a single tertiary center in northern Japan. We used the Okabayashi-Kobayashi radical hysterectomy with lymphadenectomy. We applied unilateral nerve preservation for stage IIA/IIB cancer if there was a one-sided extension of the disease outside the cervix. Indication for adjuvant therapy was based on Sedlis criteria. High-risk was defined as evidence of lymph node metastasis, pathological parametrial invasion, and a positive/close surgical margin. The choice of adjuvant therapy was chemotherapy which consisted of paclitaxel and cisplatin. RESULTS: The study included 76 early-stage IB1 (≤4 cm) and IIA1 cervical cancer and 45 locally advanced stage IB2 (>4 cm), IIA2, and IIB disease treated consecutively. The median follow-up was 106 (range: 6-203) months. There were 18 (15%) patients with recurrence, with five of 76 in the early-stage (7%) and 13 of 45 in the locally advanced disease (29%) (P<0.001). For locally advanced cervical cancer, pT classification (P<0.001), lymph node metastasis (P=0.007), and histology (P=0.05) were associated with locoregional recurrence. The five-year locoregional recurrence rate in the locally advanced disease was 20% and 5% in the early-stage disease (P=0.01). The five-year disease-free survival in the locally advanced cervical cancer was 71% and 93% in the early-stage disease (P<0.001). The overall survival in locally advanced disease depended on the adeno-type histology and lymph node metastasis. CONCLUSION: The tailored use of nerve-sparing Okabayashi-Kobayashi radical hysterectomy with adjuvant chemotherapy based on tumor histology and lymph node metastasis may be a possible option as a treatment of locally advanced cervical cancer in selected patients.

Morphofunctional cardiac changes in singleton and twin pregnancies: a longitudinal cohort study.

BACKGROUND: This study aimed to compare the echocardiographic changes and cardiac biomarkers between women with singleton and twin pregnancies. METHODS: From April 2014 to March 2016, this longitudinal cohort study invited pregnant women who were scheduled to give birth at Hokkaido University Hospital. We analyzed prospectively collected data on simultaneously determined echocardiographic parameters and blood cardiac markers of 44 women with singleton and 22 women with twin pregnancies. Furthermore, we tested the mixed-effect models for echocardiographic parameters and cardiac biomarkers. RESULTS: During the third trimester and immediately postpartum (within 1 week after childbirth), the mean left atrial volume index and brain natriuretic peptide (BNP) level were significantly higher in women with twin pregnancies than in those with singleton pregnancies. Women with twin pregnancies also had significantly smaller second-trimester inferior vena cava diameters and significantly higher third-trimester creatinine levels than those with singleton pregnancies. BNP positively correlated with the left atrial volume index (ß = 0.49, p < 0.01) and the ratio of early diastolic transmitral to mitral annular velocity (E/e') (ß = 0.41, p < 0.01). At 1 month after childbirth in women with singleton pregnancies, BNP and N-terminal precursor protein BNP (NT-proBNP) fragments immediately postpartum negatively correlated with the later E/e' (r = - 0.33, p = 0.02 and r = - 0.36, p < 0.01, respectively). CONCLUSIONS: The intravascular cardiac load reached maximum within 1 week after childbirth and was greater in women with twin pregnancies than in those with singleton pregnancies. BNP/NT-proBNP significantly positively correlated with LA volume index and E/e'. In women with singleton pregnancies, BNP secreted immediately after childbirth might improve the diastolic functions 1 month after childbirth.

Feasibility and safety of urgently initiated maternal telemedicine in response to the spread of COVID-19: A 1-month report.

AIM: In Hokkaido, Japan, the number of people suffering from coronavirus disease 2019 (COVID-19) is rapidly increased, and by the end of February 2020, there were already 70 confirmed cases of the disease. We investigated the safety of urgently initiated maternal telemedicine in preventing the spread of the coronavirus infection. METHODS: This retrospective, single-institution study examined maternal telemedicine at the department of obstetrics of the Hokkaido University Hospital from March 4 to April 2, 2020. The physicians remotely examined the pregnant women from their homes using a visual communication system which kept communication confidential, performed prenatal checkup and administered medical care according to their various blood pressures, weights and cardiotocograms. RESULTS: Forty-four pregnant women received a total of 67 telemedicine interventions. Thirty-two pregnant women (73%) had complications, and 22 were primiparas (50%). Telemedicine interventions were provided 19 times at less than 26 weeks of gestation, 43 times between 26 and 36 weeks of gestation and 5 times after 37 weeks of gestation. There was one case with an abnormality diagnosed during the remote prenatal checkups, and the patient was hospitalized on the same day. However, there were no abnormal findings observed in mothers and children during the other 66 remote prenatal checkups and medical care. CONCLUSION: Maternal telemedicine can be safely conducted in pregnant women who are at risk of having an underlying disorder or fetal abnormality 1 month following the start of the attempt. It should be considered as a form of maternal medical care to prevent the spread of COVID-19.

Survey on the use of personal protective equipment and COVID-19 testing of pregnant women in Japan.

AIM: To clarify the status of personal protective equipment (PPE) and coronavirus disease 2019 (COVID-19) tests for pregnant women, we conducted an urgent survey. METHODS: The survey was conducted online from April 27 to May 1, 2020. Questionnaires were sent to core facilities and affiliated hospitals of the obstetrics and gynecology training program and to hospitals of the national perinatal medical liaison council. RESULTS: A total of 296 institutions participated in our survey; however, 2 institutions were excluded. Full PPE was used by doctors in 7.1% of facilities and by midwives in 6.8%. Our study also determined that around 65.0% of facilities for doctors and 73.5% of facilities for midwives used PPE beyond the "standard gown or apron, surgical mask, goggles or face shield" during labor of asymptomatic women. N95 masks were running out of stock at 6.5% of the facilities and goggles and face shields at 2.7%. Disposable N95 masks and goggles or face shields were re-used after re-sterilization in 12% and 14% of facilities, respectively. Polymerase chain reaction (PCR) testing of asymptomatic patients was performed for 9% of vaginal deliveries, 14% of planned cesarean sections and 17% of emergency cesarean sections. The number of PCR tests for obstetrics and gynecology per a week ranged from zero to five in 92% of facilities. CONCLUSION: The shortage of PPE in Japan is alarming. Sufficient stockpiling of PPE is necessary to prevent unnecessary disruptions in medical care. Appropriate guidelines for PPE usage and COVID-19 testing of pregnant women at delivery are needed in Japan.

Maternal Anemia and Coagulation/Fibrinolysis after Fetoscopic Laser Photocoagulation for Twin-to-Twin Transfusion Syndrome.

AIM: This study was performed to evaluate maternal changes in laboratory characteristics after fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS). METHODS: A retrospective review was conducted among 30 women with monochorionic diamniotic twin pregnancy with TTTS who underwent FLP at 16-26 weeks of gestation. Maternal laboratory parameters were measured before and after FLP. RESULTS: The pre-FLP mean hemoglobin level (10.0 g/dL), hematocrit level (30.0%), platelet count (229 × 109/mL), fibrinogen level (461 mg/dL), and antithrombin activity (96.8%) decreased after FLP (8.5 g/dL, 25.5%, 204 × 109/mL, 403 mg/dL, and 83.6%, respectively) and returned to normal spontaneously within 2 weeks (9.6 g/dL, 29.4%, 293 × 109/mL, 460 mg/dL, and 102.4%, respectively). The D-dimer level before FLP (2.41 µg/mL) increased after FLP (4.28 µg/mL), and the elevated level was maintained for 2 weeks (3.24 µg/mL). The symptomatic venous thromboembolism (VTE) was not detected after FLP in any of the 30 patients. However, one woman had pulmonary embolism after subsequent cesarean section. CONCLUSION: Changes in maternal anemia and coagulation/fibrinolysis after FLP for TTTS returned to normal spontaneously within 2 weeks. Maternal elevation of D-dimer level after FLP might be a warning indicator of VTE.