A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome.

Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and congenital heart defects and caused by numerous germline mutations of TBX5 producing preterminal stop codons. Here, we report on a novel and unusual heterozygous TBX5 microdeletion with microinsertion (microindel) mutation (c.627delinsGTGACTCAGGAAACGCTTTCCTGA), which is predicted to synthesize a truncated TBX5 protein, detected in a sporadic patient with clinical features of HOS prenatally diagnosed by ultrasonography. This uncommon and relatively large inserted sequence contains sequences derived from nearby but not adjacent templates on both sense and antisense strands, suggesting two possible models, which require no repeat sequences, causing this complex microindel through the bypass of large DNA adducts via an error-prone DNA polymerase-mediated translesion synthesis.

Impact and Problems of Fetal Echocardiography: A Single-Institution Study in Japan.

BACKGROUND: The purpose of this study was to assess the current status of prenatal diagnosis and the benefit of fetal echocardiography for complex congenital heart disease (CHD) in Kagawa prefecture. METHOD: We reviewed 152 cases of CHDs who were born between 2012 and 2020 and performed cardiovascular surgery or catheter intervention in our hospital. They were divided into two groups: the fetal diagnosis group (FD) and the no-fetal diagnosis group (nFD). We compared patient data between FD and nFD groups. RESULTS: Of the 152 patients, 63 patients were FD group and 89 patients were nFD group. The fetal detection rate was lower than 40% between 2012 and 2014, its ratio raise to about 50% after 2015. The ratio of poor general conditions at admission was significantly higher in the nFD group (p<0.01). When focused on hypoplastic left heart syndrome, the number of patients with poor general condition at admission was significantly small in the FD group. Although, the first operation day of life and neonatal death did not show a significant difference between both groups. In total anomalous pulmonary venous connection (TAPVC) cases, 14 cases out of 15 had not been diagnosed prenatally. Among them, the number of cases with poor general condition was nine (64%) and inappropriate usage of oxygen or nitric oxide was 10 cases (71%). DISCUSSION/CONCLUSION: This study suggests that prenatal diagnosis significantly reduces poor general condition at admission. Although the prenatal detection rate grew up, that of TAPVC remains low and their clinical course is poor. In addition, inappropriate therapies were performed. It is desirable to increase the detection rate of TAPVC.

Prenatal Diagnosis of Persistent Left Superior Vena Cava Raises Suspicion for Coarctation of Aorta.

A pregnant woman was referred to our hospital with a persistent left superior vena cava (PLSVC) and a slightly smaller left heart at 35 weeks of gestation. Fetal echocardiography revealed a small aortic valve and a slightly narrow aortic isthmus. A PLSVC was identified in the dilated coronary sinus. We did not suspect strong coarctation of the aorta (CoA). Echocardiography on postnatal day 0 revealed a slightly narrow isthmus (3.1 mm with a pressure gradient of 5-10 mmHg). When the ductus arteriosus was closed, the isthmus narrowed rapidly to 2.4 mm, and the pressure gradient reached 30 mmHg, which was an indication of surgical arch repair. Aortic arch repair was performed with cardiopulmonary assistance on postnatal day 23. This case presents two lessons. First, when PLSVC is prenatally diagnosed, CoA should be suspected. Second, once CoA is suspected, careful observation of the aortic arch, particularly the isthmus, should be performed.

Investigation of the factors affecting the perinatal outcome of monochorionic diamniotic twins.

PURPOSE: To investigate the factors affecting the perinatal outcome in monochorionic diamniotic (MD) twins. METHODS: We conducted a retrospective study of MD twins treated in our hospital between April 1, 2006 and February 28, 2010. The neonatal outcomes of MD twins conceived by assisted reproductive technology or ovulation induction were compared to the outcomes of those conceived naturally. RESULTS: In MD twins with twin-to-twin transfusion syndrome (TTTS), fetoscopic laser photocoagulation (FLP) resulted in the survival of at least one twin. In naturally conceived MD twins with two live births, we found that there was a higher discordance rate and the incidence of intrauterine growth retardation was higher in twins born to nulliparous women than multiparous women. CONCLUSIONS: Further FLP treatment can be performed on twins with TTTS so that prognosis may be improved. Since the risk of discordant growth is significantly greater in twins of nulliparous women, they should be monitored more carefully than multiparous women.

Management of maternal hydrocephalus requires replacement of ventriculoperitoneal shunt with ventriculoatrial shunt: a case report.

BACKGROUND: Women with ventriculoperitoneal (VP) shunt require special care during pregnancy, although they develop few complications related to hydrocephalus. CASE: We recently encountered a pregnant patient with hydrocephalus, which was caused by VP shunt malfunction induced by increased intra-abdominal pressure associated with pregnancy. She was treated by replacement of the VP shunt with a ventriculoatrial (VA) shunt. After treatment, she achieved vaginal delivery. CONCLUSION: We recommend VA shunt implantation as a treatment option for the management of VP shunt malfunction during pregnancy. We further propose that patients in whom the VP shunt is replaced with a VA shunt can achieve spontaneous vaginal delivery.

Effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women.

OBJECTIVE: The aims of our study were to evaluate the changes in bone turnover markers during pregnancy and puerperium as a longitudinal study and to elucidate the effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women. METHODS: The study population comprised 27 Japanese pregnant women aged 23-40 years. All women were recruited for the longitudinal study from the outpatients clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. Concentrations of serum bone-specific alkaline phosphatase (BAP), urinary cross-linked type I collagen N-telopeptides (NTx), serum NTx and urinary C-terminal telopeptide of type I collagen (CTx) were measured at 10, 26, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum. In addition, we recruited 15 pregnant women (aged 25-35 years) who were treated by bed rest before 30 weeks of pregnancy for threatened premature delivery and compared bone turnover markers in these women with those in 22 normal pregnant women (aged 22-39 years). Concentrations of serum BAP, serum NTx, urinary NTx and urinary CTx were measured at 30 and 34 weeks of pregnancy and at 4 days and 1 month postpartum. RESULTS: In the longitudinal study, serum BAP concentration at 1 month postpartum was significantly higher than that at any stage of pregnancy and that at 4 days postpartum. Urinary concentration of NTx increased gradually during pregnancy and showed a peak at 36 weeks of pregnancy, followed by a decrease in the postpartum period. Serum NTx concentration and urinary CTx concentration showed the same patterns of change as that of urinary NTx concentration. In the comparison study, urinary concentrations of NTx and CTx at 30 and 34 weeks of pregnancy in women with bed rest were significantly (p<0.0001 and p<0.001, respectively) higher than those in normal pregnant women. Serum NTx concentration at 34 weeks of pregnancy in women with bed rest was also significantly (p=0.0029) higher than that in normal pregnant women. Serum BAP concentration at 34 weeks of pregnancy in women with bed rest was significantly (p=0.0038) higher than that in normal pregnant women, and these high levels were maintained during puerperium. Serum BAP concentration at 34 weeks of pregnancy was significantly correlated with duration of bed rest (r=0.767, p=0.0041). CONCLUSION: Immobilization due to bed rest during pregnancy is associated with increases in bone turnover markers in pregnant and postpartum women. Concentrations of bone resorption markers increased rapidly at the start of bed rest, while the concentration of a bone formation marker gradually increased toward puerperium.

A case of pregnancy complicated with congenital dysprothrombinemia (prothrombin Tokushima).

We present the course of pregnancy and delivery in a patient with congenital dysprothrombinemia. The patient is a 29-year-old nulliparous woman. She was diagnosed with dysprothrombinemia at 10 years of ag. Her course of pregnancy was uneventful. She delivered after prophylactic lyophilized human blood coagulation factor IX complex 800 U was administered. The plasma prothrombin activity was at 24.0% of normal plasma clotting activity. Her postpartum course was uneventful. After 6 years, her course of pregnancy was the same as before. Prophylactic lyophilized human blood coagulation factor IX complex 800 U was administered. Her plasma prothrombin activity was at 26.7%, and she underwent an induced delivery. Her postpartum course was uneventful. It is beneficial to use prophylactic lyophilized human blood coagulation factor IX complex 800 U in pregnancies that are complicated by dysprothrombinemia. The goal of therapy is to maintain prothrombin levels at above 20%.

A case of fetal parvovirus b19 myocarditis that caused terminal heart failure.

Parvovirus B19 is a well-established cause of fetal anemia and nonimmune fetal hydrops in pregnancy. Fetal parvovirus infection can cause severe destruction of erythroid progenitor cells, resulting in fetal anemia, hydrops, and intrauterine death. However, viral myocarditis with subsequent heart failure is another possible mechanism for hydrops formation as viral infection of fetal myocardial cells has been reported in postmortem examinations. We herein report a case of fetal cardiomegaly and massive pericardial effusion secondary to myocarditis as a result of parvovirus B19 infection. The case developed hydrops as consequence of severe anemia and experienced terminal heart failure, which led to the fetus dying an intrauterine death at 22 weeks of gestation. This case demonstrates that there may be an association between myocarditis caused by intrauterine parvovirus B19 infection and a poor outcome. The presence of viral myocarditis may be the determining prognostic factor in that situation.

Successful advanced maternal age pregnancy with mosaic turner syndrome conceived after ovulation induction with clomiphene citrate: a case report.

Turner women typically experience gonadal dysfunction that results in amenorrhea and sterility. We encountered a case of mosaic Turner syndrome where conception was possible after ovulation induction with clomiphene citrate (CC). The patient's ovaries were overresponsive to induction with CC. The challenges and successful outcome are reported.

Differences in insulin sensitivity in pregnant women with overweight and gestational diabetes mellitus.

AIM: The purpose of the present study was to investigate changes in insulin sensitivity using homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI) in normal-weight and overweight women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) during pregnancy. METHODS: Ninety-two pregnant women in the first trimester, 202 in the second trimester and 154 in the third trimester were enrolled in this study. Fasting plasma glucose and insulin concentrations were measured in all women in the first, second and third trimesters. HOMA indices (insulin resistance, HOMA-IR and beta-cell function, HOMA-beta) and QUICKI were calculated from fasting glucose and insulin concentrations. RESULTS: HOMA-IR values in overweight women with NGT and in women with GDM were significantly (p < 0.01) higher than those in normal-weight women with NGT. HOMA-IR in women with GDM increased significantly (p < 0.05) during pregnancy, but HOMA-IR values in normal-weight and overweight women with NGT did not change significantly with advance of gestation. QUICKI values in overweight women with NGT and in women with GDM were also significantly (p < 0.01) lower than those in normal-weight women with NGT, and QUICKI in women with GDM decreased significantly (p < 0.05) during pregnancy. HOMA-beta in normal-weight women with NGT increased significantly (p < 0.01) during pregnancy. CONCLUSION: We showed that insulin sensitivities determined by using HOMA-IR and QUICKI in overweight women with NGT and women with GDM were lower than those in normal-weight women with NGT, and that insulin sensitivity in women with GDM declined with advance of gestation.

Impact of prepregnant body mass index and maternal weight gain on the risk of pregnancy complications in Japanese women.

BACKGROUND: To analyze the association of pregnancy complications with prepregnant body mass index and weight gain during pregnancy in Japanese women. METHODS: A retrospective cohort study was conducted with 21,718 Japanese women with a singleton pregnancy. Pregnant women were grouped by prepregnant body mass index and evaluated for association with pregnancy complications using multivariate logistic regression analysis. The women in each body mass index group were then divided into groups by weight gain during pregnancy using intervals of 0.05 kg/week to analyze the relationship between the weight gain and pregnancy complications by multivariate logistic regression association analysis. RESULTS: In both nulliparous and parous women, the least pregnancy complications were found among women with medium prepregnant body mass indexes (18-23.9). Significant risks of pregnancy complications were associated with low (< 18) and high (> or = 24) prepregnant body mass indexes, particularly high prepregnant body mass indexes. In nulliparous women, the optimal weight gain was 0.25-0.4 kg/week for low (< 18) prepregnant body mass index, 0.20-0.30 kg/week for medium (18-23.9) prepregnant body mass index, and > or = 0.05 kg/week for high (> or = 24) prepregnant body mass index. In parous women, the corresponding values were > or = 0.20, 0.20-0.30, and 0.05-0.30 kg/week. CONCLUSIONS: Japanese women with prepregnant body mass indexes from 18 to 23.9 are least associated with pregnancy complications, although there is a broad range of prepregnant body mass indexes associated with few pregnancy complications. Optimal weight gain is roughly inversely related to prepregnant body mass index.

Intrauterine hemodynamic change in TTTS: the alterations in the inferior vena cava waveform in the donor fetus.

BACKGROUND: Significant hemodynamic changes are commonly observed in both fetuses in twin-twin transfusion syndrome. METHODS AND RESULTS: We describe two donor fetus cases in twin-twin transfusion syndrome associated with abnormal waveform patterns in the inferior vena cava after therapeutic amnioreduction. Subsequent echocardiographic examinations demonstrated progressive deterioration of the cardiac function in the recipient fetuses. CONCLUSIONS: We suggest that alterations in the inferior vena cava waveform in the donor fetuses may contribute to the accurate prediction of deterioration in fetal circulation after amnioreduction.