A multicenter prospective study of home blood pressure measurement (HBPM) during pregnancy in Japanese women.

In the near future, hypertensive disorders of pregnancy (HDP) have been diagnosed by home blood pressure monitoring (HBPM) instead of clinic BP monitoring. A multicenter study of HBPM was performed in pregnant Japanese women in the non-high risk group for HDP. Participants were women (n = 218), uncomplicated pregnancy who self-measured and recorded their HBP daily. Twelve women developed HDP. HBP was appropriate (100 mmHg in systole and 63 mmHg in diastole), bottoming out at 17 to 21 weeks of gestation. It increased after 24 weeks of gestation and returned to non-pregnant levels by 4 weeks of postpartum. The upper limit of normal HBP was defined as the mean value +3 SD for systolic and mean +2 SD for diastolic with reference to the criteria for non-pregnant women. Using the polynomial equation, the hypertensive cut-off of systolic HBP was 125 mmHg at 15 weeks and 132 mmHg at 30 weeks of gestation, while it for diastolic HBP was 79 mmHg at 15 weeks and 81 mmHg at 30 weeks of gestation. Systolic HBP in women who developed HDP was higher after 24 weeks of gestation, and diastolic HBP was higher during most of the pregnancy compared to normal pregnancy. When the variability of individual HBP in women developed HDP compared to normal pregnant women was examined using the coefficient of variation (CV), the CV was lower in HDP before the onset of HDP. HBPM can be used not only for HDP determination, but also for early detection of HDP.

Safety of transvaginal aspiration of cysts in pregnancies complicated with ovarian endometrioma.

OBJECTIVES: Pregnancy complicated with ovarian endometrioma is a risk factor for preterm delivery and rupture or infection during pregnancy. This study aimed to clarify the effectiveness and safety of transvaginal aspiration during pregnancy for endometrioma diagnosed in the first trimester. DESIGN: This retrospective observational study included 8 pregnant women with endometrioma who underwent transvaginal cyst aspiration at 12-14 weeks (aspiration group) between March 2011-March 2018 and 23 pregnant women with endometrioma who refused aspiration during the same period (observation group). METHODS: Characteristics of patients were compared in both groups. Safety, feasability and complications of transvaginal cyst aspiration were reported. Complications and obstetrical outcomes were reported and compared in both groups. RESULTS: The maximum cyst diameter was 8.9 ± 1.5 cm (mean ± standard deviation) in the aspiration group, which was significantly larger than that in the observation group (4.7 ± 0.2 cm). Four preterm deliveries (17.3%) occurred in the observation group and none in the aspiration group. The emergency cesarean section rate during delivery was 14.2% in the aspiration group and 43.7% in the observation group. CONCLUSIONS: The aspiration group tended to have lower rate of preterm deliveries and emergency cesarean sections, suggesting that cyst aspiration could be an effective, minimally invasive, and safe management option for endometrioma during pregnancy.

Kagami-Ogata syndrome in a fetus presenting with polyhydramnios, malformations, and preterm delivery: a case report.

BACKGROUND: Kagami-Ogata syndrome is also known as paternal uniparental disomy 14 and related disorders and is caused by abnormal genomic imprinting in the long arm of the chromosome 14q32.2 region. Its clinical manifestations include polyhydramnios in the fetal stage, respiratory insufficiency because of a small thorax, abdominal wall abnormalities, and peculiar facial features after birth. CASE PRESENTATION: A 38-year-old Japanese primigravida woman was referred to our hospital in the 19th week of pregnancy for suspected omphalocele. She had a history of hypothyroidism but was prescribed orally administered levothyroxine (50 µg/day) prior to conception and was euthyroid. Her ultrasound scan prior to visiting our hospital revealed fetal omphalocele, heavy for date, and polyhydramnios. The mother was advised to be admitted for observation from 28 weeks of gestation for threatened premature delivery. She required amniodrainage at 29 and 32 weeks of gestation. At 35 weeks of gestation, the fetal membrane prematurely ruptured and she gave birth after an emergency Cesarean section. The infant was a male child with a birth weight of 3188 g, and was suspected to have Kagami-Ogata syndrome after birth based on thoracic hypoplasia, swallowing function abnormalities, and peculiar facial features. A definitive diagnosis was established by performing genetic testing of the infant after obtaining informed written consent from both the parents; the results of the genetic testing revealed hypermethylated intergenic-differentially methylated region and maternally expressed gene 3-differentially methylated region in the corresponding chromosome 14 region. Both the parents were genetically tested after adequate genetic counseling, which revealed a de novo microdeletion in a differentially methylated region. CONCLUSION: Kagami-Ogata syndrome should have been suspected because of the presence of polyhydramnios and omphalocele during pregnancy. Respiratory insufficiency soon after birth, because of a small thorax, is expected in this disease and a diagnosis during pregnancy may have enabled appropriate care after birth.

Modified underlying cardiac disease severity in twin-twin transfusion syndrome.

Twin-twin transfusion syndrome or related conditions affect fetal loading. We report monochorionic-diamniotic twins. Twin 1 had Ebstein anomaly with mild tricuspid regurgitation (TR) and slightly thickened tricuspid valve leaflets with plastering. Twin 2 had tricuspid valve dysplasia (with abnormal thickening but without plastering) with moderate TR and mild right atrial dilatation. After birth, the severity of TR was greatly reduced in the recipient but increased in the donor. Therefore, intravascular volume change which was due to twin-twin transfusion syndrome seemed to affect the severity of the valvar disease in fetuses. This case suggests that the intrinsic severity of fetal tricuspid valvular disease may be overestimated in the recipient and underestimated in the donor twin. These factors need to be taken into consideration in clinical decision-making.

Molecular cytogenetic analysis of a hydatidiform mole with coexistent fetus: a case report.

BACKGROUND: A hydatidiform mole with a coexisting fetus is a rare condition that commonly occurs as either a partial mole with fetus or a twin pregnancy comprising a complete mole and normal fetus. In the former case, the fetus is triploid, and in the latter case, the fetus is diploid with different alleles from those of the mole. Because there is a difference in the persistent trophoblastic disease incidence between the two, an accurate diagnosis is required. CASE PRESENTATION: We present a case of a 34-year-old Japanese woman who was pregnant with a hydatidiform mole and two coexisting fetuses. At 17 weeks of gestation, hemorrhage-induced progressive anemia in the mother prompted the decision to terminate the pregnancy, after which no complications occurred. Molecular cytogenetic analysis revealed that one of the fetuses was a normal diploid fetus with the same allele in the fetus and placenta. The hydatidiform mole was revealed to be a mosaic of two diploids, and the other coexisting fetus was a normal diploid that shared one of the mole alleles. CONCLUSIONS: This was presumed to be a rare case of twin pregnancy by triploid embryo formation, followed by loss of an allele due to postzygotic diploidization, development of a diploid fetus, and development of another fetus from a separate embryo. Because of the existence of cases such as this one with a diploid fetus, but without a normal pregnancy coexistent with a complete hydatidiform mole, diagnosis by genetic analysis is required for prognosis.

Diagnosis of female 17α-hydroxylase deficiency after gonadectomy: a case report.

BACKGROUND: 17α-Hydroxylase deficiency is a recessively inherited autosomal disease caused by mutations in the CYP17A1 gene. It is a rare disease and accounts for approximately 1% of congenital adrenal cortex hyperplasias. Inhibition of 17α-hydroxylase causes low levels of cortisol and high levels of adrenocorticotropic hormone in the blood as well as excessive levels of mineralocorticoids that lead to hypertension and hypokalemia. Usually, the female patients are diagnosed with abnormality of the genitalia or extra genitalia, primary amenorrhea, or hypertension in puberty. We report a case of a 29-year-old woman who had undergone gonadectomy in her childhood due to complete androgen insensitivity syndrome and was diagnosed with 17α-hydroxylase deficiency in adulthood. CASE PRESENTATION: Our patient was a Japanese female diagnosed with androgen insensitivity syndrome, and both gonadectomy and episioplasty were performed at the age of 11 years at the University of Tsukuba Hospital. Thereafter, she was transferred to our hospital at the age of 21 years for vaginoplasty. At the age of 25 years, she presented with hypertension followed by complicated hypokalemia at the age of 28 years. The captopril loading test and adrenocorticotropic hormone loading test of her adrenal steroidogenesis revealed primary aldosteronism. After sufficient genetic counseling, a genetic test was performed that identified her as having CYP17A1 gene mutation. CONCLUSIONS: The differential diagnosis of disorders of sex development can be difficult at a young age without complete expression of the phenotype. However, diagnosis at a later age would change the treatment and prognosis of the disease; therefore, a genetic examination should be considered.

Differences in home blood pressure and pulse rates between singleton and twin pregnancies.

Objectives To evaluate home blood pressure (HBP) measurements during pregnancy and postpartum and investigate differences between singleton and twin pregnancies. Methods This prospective study involved normotensive, pregnant women who were planning to give birth at Saitama Medical Centre, Saitama, Japan between September 2013 and March 2017. HBP and pulse rate were measured twice daily and clinical blood pressure values were determined from patient records. Results HBP values were available from 101 participants; 69 women with singleton and 32 women with twin pregnancies. Systolic BP was statistically significantly higher in twin pregnancies from 23 weeks of gestation until 8 weeks after delivery compared with singleton pregnancies. Pulse rate was also statistically significantly higher between 11 and 30 weeks gestation in women with twin pregnancies compared with those with singleton pregnancies. Conclusions BP monitoring is important in the management of twin pregnancies, especially during the later gestational weeks and postpartum period and HBP would facilitate this monitoring.

Associations between the levels of soluble (pro)renin receptor in maternal and umbilical cord blood and hypertensive disorder of pregnancy.

INTRODUCTION: The prorenin (PR) receptor [(P)RR] contributes to the regulation of the tissue renin-angiotensin system (RAS) and Wnt signaling, which is involved in embryogenesis and the pathological progression of malignant tumors and diabetes mellitus. Placental (P)RR is significantly upregulated in placental tissues from preeclamptic women. However, because it cannot be examined during pregnancy, the chronological relationship between the acceleration of tissue RAS and the disease state of hypertensive disorder of pregnancy (HDP) has not been reported. In this study, we examined whether chronological changes in placental tissue RAS can be assessed by measuring soluble (P)RR [s(P)RR]. METHODS: We obtained maternal and umbilical cord blood samples from 517 pregnant women (441 singleton and 76 twin pregnancies). The concentrations of s(P)RR and prorenin (PR) were measured using enzyme-linked immunosorbent assays. RESULTS: Multivariate analysis showed that maternal serum s(P)RR levels were significantly higher in patients with HDP or fetal growth restriction (FGR) and were positively correlated with serum PR levels. Furthermore, the maternal s(P)RR level was significantly higher in HDP with severe hypertension and after the onset of HDP. However, maternal s(P)RR levels were not affected by the severity of proteinuria. Serum s(P)RR levels in umbilical cord blood of singleton pregnancies were significantly correlated with gestational week at delivery and PR level. DISCUSSION: Maternal serum s(P)RR concentrations may reflect acceleration of tissue RAS in the placenta and blood pressure severity; however, the umbilical serum s(P)RR concentration was not affected by maternal HDP.

Can biparietal diameter-to-femur length ratio be a useful sonographic marker for screening thanatophoric dysplasia since the first trimester? A literature review of case reports and a retrospective study based on 10,293 routine fetal biometry measurements.

OBJECTIVE: The aim of the study was to determine whether the biparietal diameter/femur length (BPD/FL) ratio can be used to detect thanatophoric dysplasia in the first trimester of pregnancy. MATERIALS AND METHODS: Twenty-four reported cases of thanatophoric dysplasia diagnosed based on ultrasonographic results with molecular or radiographic diagnosis were included. All sonographic measurement records were extracted and reviewed, and the BPD/FL ratio was calculated for each gestational week. In addition, 10,293 routine fetal biometry measurements from 1395 cases of patients without skeletal dysplasia were compared. RESULTS: The BPD/FL ratio in the control group decreased to less than 3 prior to gestational week 13, and to less than 2 prior to week 18. Of the 27 BPD/FL ratios obtained from 24 cases of thanatophoric dysplasia, none was in the control range. CONCLUSION: The BPD/FL ratio may be used to detect lethal skeletal dysplasias such as thanatophoric dysplasia since the first trimester.

Provisional criteria for the diagnosis of hypertension in pregnancy using home blood pressure measurements.

Most guidelines for the management of hypertension define it as a home blood pressure (HBP) value >135/85 mm Hg. However, there is no reference HBP value to diagnose hypertension in pregnant women. Therefore, in this study, we analyzed HBP measurements of pregnant women to determine whether it is appropriate to use the criteria for non-pregnant subjects for pregnant women. The participants of this study were 100 singleton pregnant women who visited our hospital between September 2013 and September 2016. We lent sphygmomanometers to the patients so they could measure their BP at home twice daily, and we measured their clinical BP when they visited the hospital. Six patients developed hypertensive disorders in pregnancy, whereas there were 63 women without hypertension or other complications that may affect BP. In the normotensive pregnant women, HBP values significantly correlated with the clinical BP values. HBP values equivalent to a clinical BP of 140/90 mm Hg, determined using the standard major axis method, were 120.8/83.5 mm Hg, 126.0/85.2 mm Hg and 136.3/89.3 mm Hg in the first, second and third trimesters, respectively. In normotensive pregnant women, HBP levels that indicate a risk of hypertensive disorder in pregnancy may be lower than 135/85 mm Hg before 28 weeks of gestation.

Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption.

AIM: Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. METHODS: This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. RESULTS: The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH < 7.00 occurred in 77.1% of patients with a decrease in fibrinogen levels to ≤ 250 mg/dL. CONCLUSION: Pre-delivery fibrinogen can predict adverse maternal as well as neonatal outcomes with placental abruption. © 2016 Japan Society of Obstetrics and Gynecology.

Expectant management of a case of uterine arteriovenous malformation with an ovarian artery aneurysm.

Uterine arteriovenous malformations are rare and their true prevalence is unknown. Selective arterial embolization is used as first-line therapy for acute severe vaginal hemorrhage associated with uterine arteriovenous malformations. However, some patients with no vaginal bleeding have been treated conservatively, so the optimal treatment modality for arteriovenous malformations is unclear. We describe a 58-year-old woman with uterine arteriovenous malformation and an ovarian artery aneurysm who was successfully treated with an expectant management approach along with an assessment of age, symptoms, and imaging findings.

Methotrexate and actinomycin D chemotherapy in a patient with porphyria: a case report.

BACKGROUND: Despite their broadly recommended use as chemotherapeutic agents, the porphyrogenicity of methotrexate and actinomycin D have not been confirmed. Accordingly, it is not known whether these agents are safe for use in patients with porphyria. CASE PRESENTATION: In this report, we present a case of an invasive mole with lung metastasis in a 49-year-old Japanese woman who had previously been diagnosed with acute intermittent porphyria at 27 years of age but had no recent history of acute intermittent porphyria attacks. Her serum human chorionic gonadotropin level was elevated 1 month after hysterectomy, and she was referred to our center for chemotherapy. After she received 100 mg of methotrexate, drug eruptions were observed starting on day 3 and grew progressively worse. Erythema and mucosal erosion spread throughout her body, whereupon she was administered prednisolone. In addition, our patient experienced febrile neutropenia and required granulocyte colony- stimulating factor treatment. No changes in our patient's urinary coproporphyrin or uroporphyrin levels were detected during this entire episode. Methotrexate was replaced by actinomycin D (0.5 mg/body intravenously on days 1-5 every 2 weeks). After five uneventful cycles of actinomycin D, our patient achieved and maintained a normal serum human chorionic gonadotropin level for 3 years. CONCLUSIONS: Methotrexate and actinomycin D did not induce acute porphyric attacks in this patient with acute intermittent porphyria; however, severe adverse effects were noted with methotrexate. Although further investigation is required, our data suggest that these agents are nonporphyrinogenic and can therefore be used to treat patients with comorbid porphyria.

The suppressive effect of dietary coenzyme Q10 on mitochondrial reactive oxygen species production and oxidative stress in chickens exposed to heat stress.

This study was conducted to determine if dietary supplementation with coenzyme Q10 (CoQ10 ), which can act as a potent antioxidant and is an obligatory cofactor of mitochondrial uncoupling protein, suppresses the heat stress (HS)-induced overproduction of mitochondrial reactive oxygen species (ROS) and oxidative damage in the skeletal muscle of birds. The carbonyl protein content of skeletal muscle was significantly higher in birds exposed to HS treatment (34°C, 12 h) than in thermoneutral birds (25°C). This increase was suppressed by CoQ10 supplementation (40 mg/kg diet). Succinate-supported mitochondrial ROS production was increased by HS treatment, and this increase was also suppressed by CoQ10 supplementation. In contrast, CoQ10 supplementation did not affect the HS-induced decrease in mitochondrial proton leak. The mitochondrial membrane potential (ΔΨ), to which HS-induced ROS production was previously shown to be sensitive, tended to be increased by HS treatment, but this rise in ΔΨ was not affected by CoQ10 supplementation. Taken together, these results suggest that dietary CoQ10 supplementation attenuates HS-induced oxidative damage to skeletal muscle, by preventing the overproduction of succinate-supported mitochondrial ROS in a manner that is independent of ΔΨ. © 2015 Japanese Society of Animal Science.

Use of intra-arterial nitroglycerin during uterine artery embolization for severe postpartum hemorrhage with uterine artery vasospasm.

OBJECTIVE: Uterine artery embolization (UAE) is a standard method for treating postpartum hemorrhage (PPH), although uterine artery vasospasm during UAE may lead to failure of hemostasis. Here, we report our experience with a case of PPH in which the bleeding was successfully controlled by intra-arterial administration of nitroglycerin during the second UAE. CASE REPORT: A 30-year-old woman experienced PPH following a successful cesarean section, and a UAE was performed. However, 6 hours later, vaginal bleeding restarted; the reason for unsuccessful embolization during the first UAE was vasoconstriction due to hypovolemic shock. We performed a second UAE, but uterine bleeding continued. After intra-arterial administration of nitroglycerin, hemostasis was confirmed, and there was no reperfusion of the uterine artery. After these two UAE procedures, no recurrence of bleeding was observed. CONCLUSION: Thus, use of intra-arterial nitroglycerin was effective for controlling uterine artery vasospasm during UAE. However, larger studies are required to confirm these findings.

Post-partum recovery course in patients with gestational hypertension and pre-eclampsia.

AIM: We examined the post-partum recovery course in patients with pre-eclampsia (PE) and gestational hypertension (GH) and evaluated the associated factors. METHODS: In a retrospective review of 145 patients with GH or PE who gave birth between 1 January 2008 and 30 October 2011 at our institution, there were 125 PE and 20 GH cases. Data collected included the gestational age at initial examination and delivery, delivery mode, time for normalization of blood pressure (BP), and time until resolution of proteinuria in PE patients. Comparisons were made between singleton and multiple pregnancies, onset (early, <32 weeks; late, ≥ 32 weeks) and fetal growth restriction in singleton pregnancies. RESULTS: The mean interval for normalization of BP was 41.8 ± 29.4 days (median, 31.5). The mean interval for resolution of proteinuria was 30.0 ± 39.6 days (median, 27.0). Ninety percent of patients required 77 and 60 days to recover from hypertension and proteinuria, respectively. The time for BP normalization was longer in the early-onset group. The time for resolution of proteinuria was not affected by any factor examined. CONCLUSION: A post-partum observation period of 12 weeks is acceptable for differentiating PE and GH from chronic hypertension or renal disease. GH severity did not affect the recovery period, but proteinuria severity did. Onset time was a factor influencing the recovery from PE and GH.