Physicians' Perspective Toward Hypertensive Disorders of Pregnancy and Future Cardiovascular Diseases in Japan.

AIM: Hypertensive disorders of pregnancy (HDP) are among the obstetric complications reportedly associated with later-life cardiovascular disease (CVD). This study examined physicians' recognition of reproductive history by elucidating their attitude and knowledge. METHODS: This study included council members of the Japan Atherosclerosis Society. An Internet-based survey was conducted between August 9 and September 9, 2022. RESULTS: A total of 137 council members completed the questionnaire (response rate: 36%). In terms of the internal medicine subspeciality of the participants, endocrinology was the most common (46%), followed by cardiology (38%). About 70% of the participants considered reproductive history to be important and obtained more information than those who considered it otherwise. In the questionnaire for knowledge about HDP and future diseases, physicians correctly answered 6.8 of 9 questions. Endocrinologists were more likely to ask regarding reproductive history at the initial visit than cardiologists (82.5% vs. 61.5%; p=0.012) and obtained more information from women below 50 years old. Contrarily, cardiologists obtained information on reproductive history from older women (those approaching menopause and those in their 60s and 70s). CONCLUSION: We found that physicians had a high level of knowledge about HDP and the importance of reproductive information. However, the manner of obtaining information, including the target population, differed depending on the subspeciality. In the future, effective interventions for women with a history of HDP need to be developed in order to encourage physicians to obtain reproductive information to prevent CVD.

Transient erythroblastopenia due to a GATA1 variant in an infant female.

Diamond-Blackfan anemia (DBA) is a congenital anemia with erythroid cell aplasia. Most of the causative genes are ribosomal proteins. GATA1, a hematopoietic master transcription factor required for erythropoiesis, also causes DBA. GATA1 is located on Xp11.23; therefore, DBA develops only in males in an X-linked inheritance pattern. Here, we report a case of transient erythroblastopenia and moderate anemia in a female newborn infant with a de novo GATA1 variant. In this patient, increased methylation of the GATA1 wild-type allele was observed in erythroid cells. Skewed lyonization of GATA1 may cause mild transient erythroblastopenia in a female patient.

Hypertensive Disorders of Pregnancy are Associated with Cardiovascular Disease in Middle- and Older-Aged Japanese Women.

AIM: Hypertensive disorders of pregnancy (HDP) are estimated to occur in up to 10% of all pregnancies and are associated with an increased risk of future cardiovascular disease (CVD) and chronic hypertension (HT). Therefore, we examined the impact of a history of HDP on CVD possibility in middle- and older-aged Japanese women. METHODS: We used the Tohoku Medical Megabank database to obtain the data of 26,024 menopausal women who were aged ≥ 50 years, had children, did not smoke, and did not have chronic kidney disease and to analyze the relationship between HDP history and CVD. RESULTS: A history of HDP was found in 4.6% of women. We divided the women into four groups according to the presence or absence of HDP and HT. The percentage of women with dyslipidemia, diabetes mellitus, and body mass index of ≥ 25 kg/m2 was the highest in the HDP＋ HT＋ group compared to the other groups (43.4%, 24.0%, and 45.2%, respectively). Adjusted odds ratio (OR) for the combined six CVD categories was higher for those with a history of HDP alone (OR [95% confidence interval [CI]]: 1.61 [1.03-2.53]). Moreover, the OR was significantly higher for those with combination with HDP history and HT (OR [95% CI]: 4.11 [3.16-5.35]). The prevalence of individual CVD was also the highest in the HT＋ HDP＋ group. CONCLUSION: An HDP history can influence the risk of CVD in Japanese women, indicating the importance of information about pregnancy outcomes in health management.

Number of Children and Risk of Cardiovascular Disease in Japanese Women: Findings from the Tohoku Medical Megabank.

AIM: Cardiovascular disease (CVD) is the second largest cause of death in Japanese women. Pregnancy and childbirth are events that put a strain on the cardiovascular system. When postpartum weight retention is insufficient, weight gain due to fat deposition during pregnancy might lead to obesity. Thus, we examined the effects of body mass index (BMI) in middle and older ages and the number of children on CVD and metabolic disorders. METHODS: From the Tohoku Medical Megabank database, we used data from 32,000 women aged ≥ 50 years. This database contains obstetrical history, medical history, and laboratory data obtained once from 2013 to 2015. RESULTS: The mean age of participants was 64.2 years, and 47.7% of women had two children. Compared with nulliparous women, those who had a higher number of children had higher BMI and systolic blood pressure. The prevalence of CVD was highest in obese class I (30 kg/m2 ≤ BMI) women with three or more children and the prevalence of hypertension was high in pre-obese (25 kg/m2 ≤ BMI ＜30 kg/m2) and obese class I women with children. Conversely, the prevalence of diabetes and proportion of women whose HbA1c values were ＞6.5% was highest in obese class I women with no children. CONCLUSION: In this study, we found that not only BMI but also the number of children influenced the health status of middle- and older-aged women, suggesting the importance of childbirth history in the health management of women.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Questionnaire dataset: Attitude of epileptologists and obstetricians to pregnancy among women with epilepsy.

This data article presents supplementary material for our report "Role of obstetricians in promoting pregnancy-related knowledge among women with epilepsy in Japan" (Egawa et al. 2020). To provide more effective preconception counseling and perinatal care, we surveyed the attitude of epileptologists and obstetricians about pregnancy-related issues in women with epilepsy (WWE). Obstetricians said they needed information from epileptologists about seizure for management of WWE. Half of epileptologists did not feel the need to communicate with obstetricians before their patients' pregnancy; they only contacted obstetricians after their patients became pregnant, and they only referred patients to an obstetrician if requested by the patient.

Role of obstetricians in promoting pregnancy-related knowledge among women with epilepsy in Japan.

The importance of informing women with epilepsy (WWE) of pregnancy-related issues when they are of reproductive age is well recognized. However, in Japan, education on pregnancy-related issues for these patients is insufficient. Obstetricians encounter patients who have self-discontinued their medications upon realizing they are pregnant. In this study, we aimed to assess the needs and understand knowledge levels regarding pregnancy-related issues among Japanese WWE. We contacted 400 board-certified epileptologists and asked them to administer our questionnaire to their patients; 51 responses were analyzed. Among all participating WWE, 100% were taking medication at the time of the study, 34% had given birth, and 63% expressed a desire to have children in the near future. Additionally, the median questionnaire score on pregnancy-related matters was as low as 9.5 out of 13 points. Only 31% of WWE knew that the mode of delivery is not always cesarean delivery. Among WWE, 62.7% stated that they had received counseling about pregnancy-related matters. Opinions differed regarding the optimum timing for counseling according to whether patients had received counseling. As for topics WWE wished to have explained to them, inheritance of epilepsy by their children ranked highly. The average satisfaction level with counseling was 5.6 of 7 points. Regarding satisfaction with counseling, there was a significant difference between WWE who expressed a desire to receive information from obstetricians and those who did not. In summary, we believe that our study shows that Japanese WWE remain ill-informed about pregnancy-related issues and that existing counseling must be revised. Obstetricians must play a role in preconception counseling.

Knowledge and attitude of hereditary breast cancer among Japanese university female students.

BRCA1/2 genetic testing to use PARP inhibitor for breast cancer has a possibility of the "secondary finding" among the younger nonaffected family members of the patient, which turns them into at-risk for hereditary breast cancer. Proper understanding of the background of the hereditary cancer is now required for appropriate acceptance of the risk. Therefore, we investigated the level of knowledge and attitudes of younger women on hereditary breast cancer in Japan. Study subject was Japanese university women between 20 and 30 years of age, without medical history of breast cancer. We conducted the anonymous self-answering questionnaire to them. We received responses from 353 women. The levels of knowledge, awareness, and interest were relatively high. Women with a family history of breast cancer were less likely to undergo testing than women without (92.8% vs. 74.5%, p < 0.001). The rates of positive response toward risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was significantly high for medical majors compared with that for other majors (RRM: medical 71.6% vs. science 54.5% vs. humanities 53.8%, p = 0.008, RRSO: 35.4% vs. 36.3% vs. 48.4%, p = 0.027). Approximately half of respondents answered that they would hesitate to get married (45.3%) or to have children (55.4%), if they were a BRCA1/2 mutation carrier. The results may help to establish the methods for supporting the decision-making for reproduction of younger women who are unexpectedly labeled as being at-risk for HBOC.

Intravenous immunoglobulin (IVIG) efficiency in women with common variable immunodeficiency (CVID) decreases significantly during pregnancy.

Immunoglobulin replacement therapy, including intravenous immunoglobulin (IVIG), is essential for pregnant women with common variable immunodeficiency (CVID) since it prevents infection and improves the health of the newborn. There are no established IVIG treatment protocols for pregnant women with CVID, and the relationship between IVIG treatment and maternal serum IgG changes during pregnancy remains unclear. Therefore, we reviewed the medical charts of four CVID patients, including one receiving subcutaneous immunoglobulin (SCIG), for IVIG dose and frequency, maternal serum IgG changes, obstetrical findings, and perinatal outcomes. There were no serious infections but one abortion and all patients continued therapy without IVIG-related adverse events. All eight children born to the patients were healthy at one month. However, the IVIG efficiency in those with CVID significantly decreased with progression of the gestational period, suggesting that IVIG dose and frequency may be changed during pregnancy to maintain stable serum IgG trough levels in women with CVID.

Obstetrical management of patients with extra-anatomic vascular bypass grafts due to Takayasu arteritis.

Little is known about the obstetrical management of patients with Takayasu arteritis (TA) who have undergone extra-anatomic vascular bypass (EAVB). We describe two cases of EAVB. Case 1 underwent EAVB due to renovascular hypertension associated with stenosis of the abdominal aorta, and Case 2 due to amaurosis fugax episodes associated with stenosis of the brachiocephalic and left common carotid arteries. Pregnancy outcomes were favorable for both cases, though the original symptoms recurred during the third trimester in each case, possibly due to increased blood flow to the pregnant uterus. Neither bypass occlusion nor anastomotic aneurysm formation was observed. Pregnancy outcomes of patients with EAVB due to TA are favorable, although pregnancies of patients with TA who have cardiovascular complications are associated with an increased risk of maternal and fetal morbidity. The obstetrical management of these patients, however, should include monitoring for complications related to the EAVB.

Chorioamniotic membrane separation after fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: The purpose of our study was to investigate the incidence of chorioamniotic membrane separation (CMS) after fetoscopic laser surgery and the association between CMS and preterm premature rupture of membranes (pPROM). We also analyzed the risk factors associated with the occurrence of CMS. METHOD: Retrospective cohort study of 148 patients with twin-twin transfusion syndrome who underwent laser surgery at our institution from March 2003 to December 2009. RESULTS: Chorioamniotic membrane separation occurred in 29 of 148 (19.6%) patients. The presence of CMS strongly correlated with pPROM prior to 28 weeks' gestation. Multivariate analysis of the risk factors of pPROM <28 w showed for CMS an odds ratio (OR) of 7.01 (95% confidence interval (CI): [1.46; 33.60], p = 0.015). Posterior placentation correlated with the occurrence of CMS (OR: 4.17, 95% CI: [1.39; 12.49], p = 0.01) and the recipient's deepest vertical pocket (OR: 1.38, 95% CI: [1.03; 1.86], p = 0.03). There was however no measurable impact of CMS on gestational age at delivery, neither on survival. CONCLUSION: Chorioamniotic membrane separation occurs in approximately 20% of patients following fetoscopic laser surgery for twin-twin transfusion syndrome and is associated with pPROM <28 w. Posterior location of the placenta coincided with an elevated risk for CMS.

Soluble (pro)renin receptor and blood pressure during pregnancy: a prospective cohort study.

The renin-angiotensin system is believed to influence blood pressure (BP) during pregnancy, but the associations between BP during pregnancy and the soluble form of the (pro)renin receptor (s[P]RR), a new component of the tissue renin-angiotensin system, remain undetermined. In this prospective cohort study of 437 pregnant women with normal BP (systolic <140 mm Hg and diastolic <90 mm Hg) during early pregnancy (<16 weeks of gestation) regression analysis was performed to examine the associations between plasma s(P)RR concentrations and BP in 3 gestational stages (20-24, 28-32, and 36-40 weeks of gestation) and logistic regression analysis to evaluate the incidence of preeclampsia. Plasma s(P)RR concentrations at early, middle (16-28 weeks), and late pregnancy (>28 weeks) and at delivery averaged 29.7 ± 10.0, 31.3 ± 12.0, 39.2 ± 8.9, and 40.4 ± 10.2 ng/mL (mean ± SD), respectively. A 1-ng/mL increase in plasma s(P)RR concentration in early pregnancy predicted systolic/diastolic BP elevation in the later 3 gestational stages: 0.11 (95% CI, 0.014-0.20)/0.093 (0.027-0.16) mm Hg for 20 to 24 weeks, 0.11 (0.029-0.19)/0.088 (0.027-0.15) mm Hg for 28 to 32 weeks, and 0.16 (0.058-0.26)/0.12 (0.043-0.19]) mm Hg for 36 to 40 weeks, respectively. Plasma s(P)RR concentrations in middle and late pregnancy were not associated with BP. Adjusted models revealed that women with plasma s(P)RR concentrations above the 75th percentile at delivery had a significantly increased risk of preeclampsia (odds ratio, 22.5 [95% CI, 1.8-279.9]). In conclusion, high circulating levels of s(P)RR at early pregnancy predicted a subsequent elevation in BP, and high concentrations at delivery were significantly associated with preeclampsia.

Increased rate of cesarean section in primiparous women aged 40 years or more: a single-center study in Japan.

PURPOSE: To investigate perinatal outcomes in late primiparous women aged 35-39 and ≥40 years. Our main research question: "Was the rate of cesarean section similar between these 2 groups of advanced maternal age?" METHODS: Primiparous women aged ≥35 years, who delivered in our center between April 2004 and March 2007, were enrolled in this study. They were divided into two groups: women aged 35-39 years and those aged ≥40 years. Antenatal complications, deliveries, and neonatal outcomes were analyzed. Fetal abnormalities, abortions, and multiple gestations were excluded. RESULTS: We assessed 752 cases (35-39 years, 610 cases; ≥40 years, 142 cases). Incidence of cesarean section (CS) was significantly higher in pregnant women aged ≥40 years (P < 0.01). The CS rate amounted to 50.0% of all deliveries in this age group. Among patients with labor deliveries, the CS rate was also significantly higher in the older age group (P < 0.05). With regard to indication for CS with labor deliveries, the rate of non-progressive labor/dystocia was 19.4% in primiparous women aged ≥40 years and 11.0% in those aged 35-39 years, respectively (P < 0.05). In contrast, the rates of antenatal complications were not different between the two groups, except for gestational diabetes or leiomyoma. No significant differences between the two groups could be found for neonatal outcomes such as birth weight, Apgar score, and admission to neonatal intensive care unit. CONCLUSIONS: CS rate was 50.0% in primiparous women aged ≥40 years. In addition, CS caused by dystocia was almost twice as frequent in primiparous women aged ≥40 years as in women aged 35-39 years. Among late pregnancies, primiparous women aged 40 years and older had higher risk of CS.

[Recurrent ovarian cancer with cancer peritonitis treated with weekly paclitaxel infusion--a clinicopharmacological study].

We treated a patient with recurrent ovarian cancer with cancerous peritonitis by weekly paclitaxel (w-TXL) therapy (65 mg/m2). Abdominocentesis was not performed to eliminate ascites, in order to maintain higher quality of life (QOL), and critical adverse reaction was not seen for 12 months. We measured the TXL concentration in blood plasma and ascites after TXL infusion by HPLC method. The TXL titer in plasma was 427 ng/ml after infusion, 23 ng/ml after 24 hours and under 10 ng/ml after 48 hours. The TXL titer in ascites was 41 ng/ml after infusion, 37 ng/ml after 6 hours, 18 ng/ml after 12 hours, 10 ng/ml after 24 hours and under 10 ng/ml after 48 hours. TXL transportation from blood to ascites was good. This result suggested that intravenous infusion of TXL was effective for cancerous peritonitis treatment.

[A case of ovarian cancer with Parkinson's disease treated by combined chemotherapy with paclitaxel and carboplatin followed by surgery].

It is well known that neuropathy, myelopathy, and arthropathy are specific adverse effects induced by paclitaxel administration. Parkinson's disease is neural degenerative disease, and the influence of paclitaxel administration on patients with Parkinson's disease is unknown. We have successfully treated an ovarian cancer patient with Parkinson's disease by paclitaxel/CBDCA combined chemotherapy after surgery. The patient was a 57-year-old woman with solid and cystic ovarian tumor. Among the tumor markers CA125, CA19-9, and SLX, only SLX was elevated. We operated and made a pathological diagnosis of the ovarian tumor as clear cell adenocarcinoma (FIGO stage Ic). After surgery, the patient was treated with paclitaxel (260 mg [175 mg/m2]) and CBDCA (600 mg [AUC = 5]) combined chemotherapy for 5 courses. Her status is complete remission. During chemotherapy, she had felt the decreased efficacy of her Parkinson's disease medication. We could continue chemotherapy by increasing the dose of the Parkinson's drug. There is only one case report on the influence of paclitaxel on Parkinson's disease, in which the course was similar to the present case.