Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan.

AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.

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Case 1 presented with severe anemia and received an intrauterine blood cell transfusion at 33 weeks of gestation. The anemia spontaneously improved in early infancy. Case 2, the father of Case 1, had an uneventful birth with no evidence of anemia, though microcytic anemia was observed during childhood. The genetic analysis of the ß-globin gene cluster identified a novel heterozygous deletion of DNA extending from the Gγ-globin gene downstream to the ß-globin gene, confirming a diagnosis of (G γA γδß)0 -thalassemia. In cases where thalassemia is suspected based on blood tests, a genetic diagnosis should be performed for the sake of the offspring.

High maternal mortality rate associated with advanced maternal age in Japan.

This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3-4.7) for < 20 years, 2.6 (95% CI 1.7-3.8) for 20-24 years, 2.9 (95% CI 2.3-3.6) for 25-29 years, 3.9 (95% CI 3.3-4.5) for 30-34 years, 6.8 (95% CI 5.9-7.9) for 35-39 years, and 11.2 (95% CI 8.8-14.3) for ≥ 40 years of age. Patients who were ≥ 40 years of age had a significantly higher mortality rate compared to that in other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54%]) was the most common cause of hemorrhagic stroke. Maternal mortality is significantly higher in older than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women > 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.

Placental recruitment after spontaneous single fetal demise in monochorionic diamniotic twin pregnancies.

INTRODUCTION: The incidence of single fetal demise in monochorionic diamniotic twin pregnancies is approximately 7.5%. In single fetal demise cases, the placental region of the demised fetus is almost infarcted or necrotic at the time of delivery. Further, it has been reported that in some cases, a surviving fetus uses all regions of the placenta after a single fetal demise. Thus, in the present study, we investigated the incidence and natural prognosis of placental recruitment in spontaneous single fetal demise cases over a period of 11 years. METHODS: All 306 monochorionic diamniotic twin pregnancies that were delivered between 2011 and 2021 in our institution were included in this retrospective cohort study. The placenta and umbilical cord were investigated, and the type of anastomosis was identified by color injection. Furthermore, the number and direction of arteriovenous anastomoses were recorded. RESULTS: There were eight single fetal demise cases, excluding cases of twin-reversed arterial perfusion sequence and after fetoscopic laser photocoagulation. The placental region of six demised fetuses had an infarction or necrotic region. In two cases, an infarction or necrosis was not observed, and the surviving fetus used all regions of the placenta. DISCUSSION: The surviving fetus in monochorionic diamniotic twin pregnancies with superficial anastomoses can use all regions of the placenta, even after a spontaneous single fetal demise. Further studies are needed to determine the difference between such cases and in those in which only the localized regions of the placenta can be used.

Intestinal volvulus in utero causing torsion of dilated bowel with ileal atresia: a case report.

BACKGROUND: In utero intestinal volvulus with intestinal atresia is a rare and life-threatening condition that can cause torsion of the dilated bowel. The management and outcomes of this disease remain unclear. CASE PRESENTATION: A 19-year-old woman noticed a decrease in fetal motion at 35 weeks. Fetal ultrasound showed dilated fetal bowel and the whirlpool sign. The patient was referred to our hospital for an emergency cesarean section. The neonate's abdomen was dark and severely distended, and a laparotomy was performed. Necrotic ileum and cord-type intestinal atresia (Type II) were observed in the dilated terminal ileum. The necrotic ileum was resected, and a second-look surgery was performed the following day. Then, we anastomosed the remaining intestine, and the total intestine length was 52 cm. There were no surgical complications, and the patient was discharged without requiring total parenteral nutrition or fluid infusion. The patient's height and weight were within the - 2 standard deviation range of the growth curve at 5 months. CONCLUSIONS: Emergency and appropriate management of intestinal volvulus in utero causing torsion of the dilated bowel resulted in good outcomes in a patient with intestinal atresia. Perinatal physicians should be aware of this emergency condition and plan their treatment approach accordingly.

Pregnancy-related maternal deaths due to cardiovascular diseases in Japan from 2010 to 2019: an analysis of maternal death exploratory committee data.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of maternal deaths in high-income countries. This study aimed to assess the characteristics of maternal deaths due to CVDs and the quality of care provided to patients, and to identify elements to improve maternal care in Japan. METHODS: This descriptive study used the maternal death registration data of the Maternal Deaths Exploratory Committee of Japan between 2010 and 2019. RESULTS: Of 445 eligible pregnancy-related maternal deaths, 44 (9.9%) were attributed to CVD. The most frequent cause was aortic dissection (18 patients, 40.9%), followed by peripartum cardiomyopathy (8 patients, 18.2%), and pulmonary hypertension (5 patients, 11.4%). In 31.8% of cases, cardiopulmonary arrest occurred within 30 min after initial symptoms. Frequent symptoms included pain (27.3%) and respiratory symptoms (27.3%), with 61.4% having initial symptoms during the prenatal period. 63.6% of the patients had known risk factors, with age ≥35 years (38.6％), hypertensive disorder (15.9%), and obesity (15.9%) being the most common. Quality of care was assessed as suboptimal in 16 (36.4%) patients. Cardiac risk assessment was insufficient in three patients with preexisting cardiac disease, while 13 patients had symptoms and risk factors warranting intensive monitoring and evaluation. CONCLUSION: Aortic dissection was the leading cause of maternal death due to CVDs. Obstetrics care providers need to be familiar with cardiac risk factors and clinical warning signs that may lead to impending fatal cardiac events. Timely risk assessment, patient awareness, and a multidisciplinary team approach are key to improving maternal care in Japan.

Doppler Waveform Analysis of Intertwin Venous Blood Flow in Twin Reversed Arterial Perfusion (TRAP) Sequence with a Rudimentary Heart.

Twin reversed arterial perfusion (TRAP) sequence is a rare anomaly in 1% of monochorionic twin pregnancies. Few TRAP sequence cases have a rudimentary heart with cardiac motion in the acardiac twins. Herein, we investigated the venous Doppler waveform in two cases of TRAP sequence with a rudimentary heart with cardiac motion in the acardiac twin. Although both cases had veno-venous anastomoses, the venous Doppler waveforms of the umbilical vein differed. A comparison of the characteristics of the cases indicated that the existence of a ductus venosus, or greater heart pulse power, in the acardiac twin might impact the venous Doppler waveform in the pump twin.

Perinatal outcome in case of maternal death for cerebrovascular acute disorders: a nationwide study in Japan.

OBJECTIVE: The goal of this study is to find clues to improve perinatal outcomes in the case of cerebrovascular acute disorders during pregnancy. STUDY DESIGN: We analyzed 35 cases of cerebrovascular diseases related to maternal deaths in Japan those that occurred during pregnancy and reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2018. RESULTS: Cerebrovascular acute disorders occurred at 34.6 ± 6.6 gestational weeks. There were seven intrauterine fetal deaths (IUFD), and eight cases showed neonatal asphyxia with umbilical arterial pH between 6.7 and 7.0 (asphyxia cases, n = 15). In two of eight newborns, brain hypothermia therapy was given, and all survived without neurological sequelae. Maternal dyspnea was significantly related to severe prolonged decelerations of the fetus (p < .05), and asphyxia cases (p < .005). Median time from maternal onset to delivery (OD time) was significantly longer in asphyxia cases than in the non-asphyxia cases (84 vs 29 min, p < .05). OD time over 30 min was significantly related to the antepartum occurrence, cervical dilatation <5 cm (p < .05), onset outside of the hospital (p < .001), and maternal transfer before delivery (p < .001). CONCLUSION: More than 40% of cases experienced fetal asphyxia, and 20% ended in IUFD in maternal deaths related to cerebrovascular acute disorders. Maternal respiratory support and rapid delivery would be the keys to improve perinatal outcomes in case of cerebrovascular acute disorders during pregnancy.

Effect of Superficial Anastomoses on Circulatory Dynamics in Twin-Twin Transfusion Syndrome.

The role of superficial anastomoses in the survival of fetuses with twin-twin transfusion syndrome after fetoscopic laser photocoagulation is unknown. This study aimed to evaluate how superficial anastomoses affect the circulatory dynamics of both fetuses with twin-twin transfusion syndrome using ductus venous Doppler waveforms. We included all twin-twin transfusion syndrome (TTTS) patients who underwent fetoscopic laser photocoagulation in our institution from 2006 to 2019; fetal demise cases after fetoscopic laser photocoagulation were excluded. We recorded ductus venous Doppler waveforms on the same day or one day before fetoscopic laser photocoagulation and one day after fetoscopic laser photocoagulation and measured the ductus venous pulsatility index and velocity ratios. We compared these z-scores of donor and recipient twins between a group without superficial anastomoses and the groups with arterio-arterial or veno-venous anastomoses. A total of 115 surviving TTTS placentas after fetoscopic laser photocoagulation were analyzed. The ductus venous pulsatility index and all ratios were better in recipient twins with arterio-arterial anastomoses than in those without. The a-wave-related ratios were better in recipient twins with veno-venous anastomoses than in those without. Superficial anastomoses reduced the blood volume and arterio-arterial anastomoses protected the diastolic cardiac function in recipient twin-twin transfusion syndrome twins before fetoscopic laser photocoagulation. Superficial anastomoses in TTTS equilibrate blood pressure between donor and recipient twins.

Dose-Dependent Influence of Antithyroid Drugs on the Difference in Free Thyroxine Levels between Mothers with Graves' Hyperthyroidism and Their Neonates.

BACKGROUND: Several guidelines have recommended that the use of the lowest effective dose of antithyroid drugs (ATDs) that maintains maternal serum free thyroxine (FT4) levels at or moderately above the upper limit of the reference range is appropriate for fetal euthyroid status. However, little is known about whether ATD dosage affects the difference in serum FT4 levels between the mother and neonate. We conducted a retrospective study at a tertiary hospital in Japan to investigate the dose-dependent influence of ATDs on both maternal and fetal thyroid hormone status. MATERIALS AND METHODS: We retrospectively examined 62 pregnant women who delivered between 2007 and 2016 and were treated for Graves' hyperthyroidism with ATD at any stage during pregnancy. We selected individuals whose data on maternal FT4 level within 4 weeks of their deliveries and cord FT4 level of their infants at the time of delivery were available. Those with multiple pregnancies, iodine or glucocorticoid treatment, and fetal goiter detected by ultrasonography were excluded. RESULTS: After the exclusion criteria were applied, we recruited 40 individuals. The cord FT4 levels were significantly lower than the maternal FT4 levels in patients treated with high-dosage ATDs (methimazole >5 mg daily or propylthiouracil >100 mg daily). However, there were no significant differences between maternal and cord FT4 levels in patients treated with low-dosage ATDs (methimazole ≤5 mg daily or propylthiouracil ≤100 mg daily). We selected 35 individuals whose data on maternal thyrotropin receptor-binding inhibitory immunoglobulin (TBII) level were available. Multiple linear regression analysis adjusted for ATD dosage, maternal TBII level, and gestational period found that ATD dosage was a significant predictor of the difference in serum FT4 levels between the mother and neonate. In terms of maternal complications, multiple logistic regression analysis identified maternal free triiodothyronine (FT3) level as a significant predictor of the incidence of preterm delivery. CONCLUSIONS: We found a dose-dependent influence of ATDs on the difference in serum FT4 levels between mothers with Graves' hyperthyroidism and their neonates. Further studies to evaluate the optimal target FT4 and FT3 levels for the mother and neonate during pregnancy may improve the outcome of pregnant women with Graves' hyperthyroidism.

Changes in the Ultrasonographical Appearance of Intertwin-Dividing Membrane of Monochorionic Diamniotic Twin Pregnancy.

Ultrasound determination of chorionicity in the first trimester has a high accuracy, but it is associated with some pitfalls. This report presents changes in ultrasound findings during a monochorionic pregnancy with chorionic membrane folding (CMF). The patient was a 32-year-old woman, gravida 2 para 0. Her transvaginal ultrasonography identified two gestational sacs (GSs) and two embryos at 7 weeks of gestation. At 9 weeks' gestation, an ultrasound image showed a lambda sign at both sides and the interruption of chorionic membranes, resulting in the diagnosis of a monochorionic diamniotic (MCDA) twin pregnancy with CMF. At 11 weeks' gestation, an ultrasound image showed a lambda sign at one portion of the septum and a T sign at another portion. This change suggested that the folded chorionic membrane had partially flattened. At 35 weeks' gestation, an emergency cesarean section was performed. Two healthy male neonates were delivered. Histological placental examination confirmed that the intertwin membrane was composed of two amniotic membranes without a folded chorionic membrane, confirming the diagnosis of a MCDA twin pregnancy. This case presents two important ultrasound chorionicity findings: a monochorionic pregnancy with CMF can show two GSs and a lambda sign and the CMF can flatten or change during the pregnancy.

Nationwide survey of intrauterine blood transfusion for fetal anemia in Japan.

AIM: The present study investigated the current situation regarding intrauterine blood transfusion (IUT) for fetal anemia in Japan. METHODS: We conducted a nationwide, multicenter, retrospective cohort questionnaire survey for cases that underwent IUT from 2011 to 2015. The questionnaire required perioperative information, indications, details of the procedure, procedure-related complications, and neonatal morbidity. RESULTS: A total of 100 IUT procedures were performed in 66 cases at 19 institutions during the study period. The most frequent indication of IUT was complicated monochorionic diamniotic (MCDA) twins in 28 (42.4%) cases, followed by 16 (24.2%) cases of red-cell alloimmunization, and 10 (15.2%) cases of parvovirus B19 infection. IUT was performed through the umbilical cord in the vast of majority cases (92%). Bleeding from the IUT site was the most common adverse event (40%). Two cases (2%) underwent emergency cesarean section after the procedure. There were no cases of rupture of membrane or intrauterine infection after IUT. The neonatal survival rate was 77.3% in the 66 total cases and 64% in the hydrops cases. The neonatal survival rates in MCDA twins, red-cell alloimmunization, and parvovirus B19 infection were 75%, 93.8%, and 70%, respectively. CONCLUSIONS: IUT was performed for mainly three indications in Japan: MCDA twins, red-cell alloimmunization, and parvovirus B19 infection. The incidences of severe adverse events seemed very low. The outcomes after IUT were favorable with variations in survival rates according to indications. However, further studies with long-term follow-up will be required to assess the effectiveness of IUT, especially for complicated MCDA twins.

Analysis of preventability of malignancy-related maternal death from the nationwide registration system of maternal deaths in Japan.

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II-IV in 9, and the performance status was 3-5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24-30] (19-40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant.

Nationwide study of mortality and survival in pregnancy-related streptococcal toxic shock syndrome.

AIM: Streptococcal toxic shock syndrome is associated with the highest infection-related maternal mortality rates. We conducted a comparative analysis of the background factors and treatment course between survivors and nonsurvivors to improve our understanding concerning the optimal initial treatment approach for this fulminant disease. METHODS: This retrospective observational study was conducted based on clinical data collected from two national organizations. Clinical data of patients who died or survived (i.e. background information, clinical course and treatment administered) were collected. RESULTS: Records of 13 dead and 15 surviving patients were collected and analyzed. No statistically significant differences were found between the groups regarding age, parity, season, gestational age or the patients' location at the onset of symptoms. After the initial symptom onset, the survivors received antibiotics more systematically during their first visit to a clinic (P = 0.006). More survivors had received treatment within 1 h of onset of fulminant disease (P = 0.069). The number of fetal deaths was significantly higher in the mortality group (P = 0.003), while the fetal survival number was higher in the group of maternal survivors (P = 0.055). Maternal survivors with nonspecific initial symptoms received early intervention when there was a family history of group A streptococcal infection or a positive rapid antigen test result. CONCLUSION: Intensive care, including systemic antibiotic administration, may contribute to maternal survival when administered immediately (within 1 h) after the fulminant streptococcal toxic shock syndrome onset. Eliciting a family history of streptococcal infection and conducting a rapid antigen test can identify the patients needing early intervention.

"En Caul" Cesarean Delivery for Extremely Premature Fetuses: Surgical Technique and Anesthetic Options.

The risks and technical difficulties at the cesarean delivery for extremely premature infant under 1,000g are as follows: (1) a premature infant is very weak for pressure of uterine wall or human hands, (2) skin of infant is really premature and weak, (3) uterine wall is thick and difficult to incise at lower segment of uterus, (4) classical vertical incision or reverse T-shape incision are at risk for future uterine rupture, and (5) at the timing of rupture of membrane, uterine wall may contract drastically and the infant is trapped the uterine wall, so called "hug-me-tight-uterus". To resolve the problems, we use the technique of "En Caul" cesarean delivery with nitroglycerin. Intravenous injection of nitroglycerin just before uterine incision made the rapid and sufficient relaxation of uterine muscle. After getting adequate uterine relaxation, U- or J-shaped incision is made to lower segment of the uterus; however, we never incise the membrane before the infant was delivered. The baby is delivered with wrapped amniotic fluid and the membrane, which protect the infant against the pressure of uterine wall or surgeon's hands. The infant is gently handled to neonatologist by "En Caul" with the placenta. Neonatologist can make the membrane ruptured and resuscitation. Own blood transfusion can be made through the umbilical cord and placenta, if the infant was anemic or hypovolemic.

Perinatal outcomes of intrauterine transfusion for the surviving twin in monochorionic twin gestation involving a single fetal demise.

AIM: This study aimed to evaluate the feasibility and outcome of intrauterine transfusion (IUT) for the surviving co-twin in monochorionic diamniotic (MCDA) twin gestations involving single intrauterine fetal death (sIUFD). METHODS: Cases of MCDA twin gestations involving emergent IUT for co-twins experiencing acute feto-fetal hemorrhage (AFFH) subsequent to sIUFD during the second trimester were reviewed. Fetal anemia was confirmed via fetal blood sampling, and perinatal data were retrieved from medical charts to determine the outcomes of surviving co-twins. A poor outcome at 28 days of age was defined as fetal death, neonatal death or neurological impairment such as severe intraventricular hemorrhage or cystic periventricular leukomalacia (PVL). RESULTS: This study included 16 cases of sIUFD diagnosed at a median of 22.5 weeks of gestation (range: 18-25 weeks). The median interval in hours between diagnosis of fetal demise and IUT was approximately 4.2 (0-22) hours. All cases achieved IUT without significant intraoperative complications. Four cases experienced a fetal loss of the co-twin, whereas 12 co-twins were born alive (including 9 preterm births), with only 1 poor outcome in a preterm infant with PVL. CONCLUSION: IUT may be a feasible prenatal intervention for surviving co-twins with AFFH. However, more extensive or pooled studies are needed to determine the efficacy of this intervention.

The Incidence of Dichorionic Diamniotic Twin Pregnancy After Single Blastocyst Embryo Transfer and Zygosity: 8 Years of Single-Center Experience.

Dichorionic diamniotic (DCDA) twin pregnancies after single blastocyst embryo transfer have been reported recently, although a blastocyst ovum is generally believed to divide into monochorionic twin pregnancy. We investigated the incidence of DCDA twin pregnancy after single blastocyst embryo transfer and their zygosity. This prospective cohort study included 655 consecutive twin pregnancies that were managed from 2006 to 2014 at our institution. Chorionicity and amnionicity were determined using first-trimester ultrasonography and/or placental pathology. Zygosity was analyzed if the cases were DCDA twins after single blastocyst embryo transfer. Among 655 twin pregnancies, there were 348 DCDA cases, 295 monochorionic diamniotic (MCDA) cases and 12 monochorionic monoamniotic cases. Single blastocyst embryo transfer was performed in 43 cases. Six out of the 43 (14%) cases involved DCDA twin pregnancies and the other 37 cases involved MCDA twin pregnancies. Three DCDA twins born after single blastocyst embryo transfer, wherein frozen embryo transfer (FET) was performed in the natural cycle, were dizygotic, and the other three cases, wherein FET with hormone replacement therapy was performed, were monozygotic. DCDA twin pregnancy occurred in 14% (7% for monozygotic and 7% for dizygotic) of twin pregnancies after single blastocyst embryo transfer cases.