Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus.

UNLABELLED: The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. CONCLUSIONS: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.

MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin ß1 pathway.

OBJECTIVE: Mucin (MUC) 20 has recently been implicated to play a role in human carcinogenesis. However, the role of MUC20 in epithelial ovarian cancer (EOC) remains to be elucidated. METHODS: MUC20 expression was assessed in tissue microarray and tumor specimens of EOC patients by immunohistochemistry. Effects of MUC20 on cell viability, adhesion, migration, and invasion were analyzed in MUC20 overexpressing or knockdown EOC cells. Western blotting was performed to analyze signaling pathways modulated by MUC20. RESULTS: MUC20 was overexpressed in EOC samples compared with benign tissues. High MUC20 expression was significantly associated with poor overall survival in patients with advanced-stage disease. MUC20 overexpression significantly enhanced EOC cell migration and invasion, but not viability. Mechanistic investigations showed that MUC20 increased cell adhesion to extracellular matrix (ECM) proteins and enhanced activation of integrin ß1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin ß1 signaling by MUC20 was significantly suppressed by integrin ß1 blocking antibody. Furthermore, these effects of MUC20 on EOC cells were also demonstrated in MUC20 knockdown cells. CONCLUSIONS: Our results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin ß1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.

Group B streptococcus antimicrobial resistance in neonates born to group B streptococcus-colonized mothers: Single-center survey.

AIM: In this study, we collected group B streptococcus (GBS) screening data and analyzed screening rate, antimicrobial resistance rate, and neonatal observation room (NOR) admission rate due to inadequate chemoprophylaxis. METHODS: The GBS screening data for January 2006-December 2013 were retrospectively collected and analyzed. We also collected data for neonates admitted to NOR due to inadequate chemoprophylaxis during the period 1 April 2010-31 December 2013. RESULTS: A total of 12 200 pregnant women received rectovaginal culture during the 8-year study period. The overall screening rate was 53.8% and maternal colonization rate was 20.7%. The GBS screening rate increased remarkably, from 23.2% in 2006 to 70% in 2013. Antimicrobial resistance was common. The resistance rates for each antimicrobial used in pregnancy were as follows: clindamycin, 49.51%; erythromycin, 49.51%. A total of 297 neonates were admitted to NOR due to inadequate antibiotic prophylaxis during 1 April 2010-31 December 2013. The overall NOR admission rate due to inadequate chemoprophylaxis was 2.67%, and the inadequate chemoprophylaxis rate for those GBS colonized mothers was 19.6%. None of these 297 infants had positive blood culture for GBS sepsis. CONCLUSION: The GBS screening rate increased remarkably, reaching 70% in 2013. The NOR admission rate due to inadequate chemoprophylaxis was 2.67% and there was no early onset GBS disease in a total of 11 123 deliveries in this 4-year cohort study.

Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV.

BACKGROUND & AIMS: Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. METHODS: We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5-10 years old. RESULTS: A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). CONCLUSIONS: Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.

MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer.

OBJECTIVE: Mucins play a critical role in the malignancy of various tumors and have been identified as diagnostic markers and as attractive therapeutic targets. However, the role of mucin (MUC) 20 in endometrial cancer (EC) is still unknown. METHODS: The relationship between MUC20 expression and clinical characteristics of EC was analyzed in 97 EC tumors and 16 normal tissues by immunohistochemistry. Effects of MUC20 on EC cells, HEC-1A and RL95-2, were examined by in vitro cell growth, migration, and invasion assays, as well as in vivo tumor growth in SCID mouse model. Western blotting was performed to analyze signaling pathways modulated by MUC20. RESULTS: MUC20 expression was significantly higher in EC tumors compared with the normal tissue. High levels of MUC20 expression in EC tumors were correlated with an unfavorable histologic subtype. Furthermore, MUC20 was an independent prognostic factor for poor survival as evaluated by multivariate analyses. Overexpression of MUC20 in EC cells significantly enhanced cell growth, migration, and invasion, as well as tumor growth in vivo. The MUC20-enhanced invasive behavior was significantly blocked by erlotinib, an EGFR inhibitor. Moreover, MUC20 overexpression enhanced EGF-mediated migration and invasion, suggesting a critical role of EGFR in MUC20-mediated effects. We found that MUC20 overexpression could enhance EGF-induced phosphorylation of EGFR and STAT3. Inhibition of the STAT3 activity by its inhibitor Stattic significantly suppressed the MUC20-enhanced invasive behavior. CONCLUSIONS: MUC20 is novel prognostic factor for EC and its overexpression enhances EGF-triggered invasive behavior through activation of EGFR-STAT3 pathway.

Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro.

AIM: To investigate whether sphingosine-1-phosphate (S1P), a potent angiogenic factor, induced vascular endothelial growth factor-C (VEGF-C) expression in endothelial cells in vitro and to examine its underlying mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were examined. VEGF-C mRNA expression in the cells was assessed using real-time PCR. VEGF-C protein and FGFR-1 phosphorylation in the cells were measured with ELISA. RNA interference was used to downregulate the expression of matrix metalloproteinase-2 (MMP-2), fibroblast growth factor-1 (FGF-1) and FGF receptor-1 (FGFR-1). RESULTS: Incubation of HUVECs with S1P (1, 5, and 10 µmol/L) significantly increased VEGF-C expression. The effect was blocked by pretreatment with the MMP inhibitor GM6001 or the FGFR inhibitor SU5402, but not the EGFR inhibitor AG1478. The effect was also blocked in HUVECs that were transfected with FGFR-1 or MMP-2 siRNA. Furthermore, incubation of HUVECs with S1P (5 µmol/L) significantly increased FGFR-1 phosphorylation, which was blocked by GM6001. Moreover, knockdown of FGF-1, not FGF-2, in HUVECs with siRNAs, blocked S1P-induced VEGF-C expression. CONCLUSION: S1P induces VEGF-C expression through a MMP-2/ FGF-1/FGFR-1-dependent pathway in HUVECs.

Temporal transition trends of cord blood lead levels in various human development index countries and in the Taipei metropolitan area.

Since low-level lead exposure is still of concern for neonates, it is worth further characterizing the temporal transition trends of cord blood lead levels (CBLLs) globally and locally in Taipei, Taiwan, after the cessation of leaded gasoline use. A literature review on CBLLs around the world was performed by searching three databanks, i.e., PubMed, Google Scholar and Web of Science, with the search keywords "cord blood" combined with "lead" or "Pb" for studies published from 1975 to May 2021. In total, 66 articles were included. Linear regressions for the reciprocal of sample size weighed CBLLs against calendar year presented a high r2 value (0.722) for the very high Human Development Index (HDI) countries and a moderate r2 value (0.308) for the combined high and medium HDI countries. The predicted CBLLs in 2030 and 2040 were 6.92 (95% CI: 6.02-7.81) µg/L and 5.85 (95% CI: 5.04-6.66) µg/L, respectively, for the very high HDI countries and 13.10 (95% CI: 7.12-19.09) µg/L and 10.63 (95% CI: 5.37-15.89) µg/L, respectively, for the combined high and medium HDI countries. To characterize the CBLL transitions in the Great Taipei metropolitan area, data from five studies conducted from 1985 to 2018 were employed. Although the results of the early four studies indicated that the Great Taipei metropolitan area did not reach the pace in CBLL reduction among the very high HDI countries, the CBLLs of the latest study during 2016-2018 were pretty low (8.1 ± 4.5 µg/L), approximately 3 years in advance of the very high HDI countries as one group to reach this low CBLL. In conclusion, further effective reduction in environmental lead exposure is challenging and must be based on the efforts from the aspects reflected by the HDI index compositions, i.e., economics, education and health, mostly implying health disparity and inequality.

Depressive symptoms as a predictor of sexual function during pregnancy.

INTRODUCTION: Biopsychological and sociocultural factors have been reported to be associated with sexual function in pregnancy. To date, very few studies have focused on the relationship between sexual function and depression during pregnancy. AIM: To determine whether depressive symptoms predict overall sexual function, desire, arousal, lubrication, orgasm, satisfaction, and pain during pregnancy by using the Female Sexual Function Index (FSFI). METHODS: Pregnant women undergoing prenatal examinations were randomly selected for this cross-sectional investigation. The study included 555 pregnant women who completed the Taiwanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D), FSFI, and a demographic questionnaire during pregnancy. MAIN OUTCOME MEASURES: CES-D scores for depressive symptoms, scores for overall sexual function on the FSFI, and the FSFI domains: desire, arousal, lubrication, orgasm, satisfaction, and pain. RESULTS: After adjusting for demographic factors, CES-D scores during the first trimester negatively predicted overall sexual function (P=0.0004), arousal (P=0.0104), lubrication (P=0.0016), orgasm (P=0.0022), and pain (P<0.0001). Moreover, CES-D scores during the third trimester negatively predicted sexual desire (P=0.0005) and satisfaction (P<0.0001). Furthermore, gestational age negatively predicted overall sexual function, arousal, lubrication, orgasm, and pain (all P<0.0001). Parity was a positive predictor of overall sexual function, arousal, lubrication, and orgasm (all P<0.0005). Medical conditions were positive predictors of sexual desire (P=0.0023). CONCLUSIONS: The present study revealed that depressive symptom scores during early and late pregnancy were significant negative predictors of sexual function during pregnancy.

Hypoxia-mediated down-regulation of OCTN2 and PPARα expression in human placentas and in BeWo cells.

The objective of the present study was to investigate the effects of hypoxia on placental expression of OCTN2 and PPARα. OCTN2 and PPARα expression in the human placenta in the presence or absence of preeclampsia was examined by immunohistochemical (IHC) analysis, Western blotting, and quantitative polymerase chain reaction (qPCR). Effects of hypoxia on the expression of OCTN2 and PPARα in human placental explants and human choriocarcinoma BeWo cells were examined by Western blotting and qPCR analyses. IHC, Western blot, and qPCR studies showed that OCTN2 and PPARα protein and mRNA levels were lower in syncytiotrophoblasts from preeclamptic human placentas than in those from normal placentas. Hypoxic treatment caused a decrease in OCTN2 and PPARα expression in human placental explants and in BeWo cells. WY14643, a PPARα agonist, caused an increase in OCTN2 expression in BeWo cells under hypoxic conditions. In conclusion, under hypoxic conditions, placental OCTN2 is down-regulated through PPARα-mediated pathways.

Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells.

Mucins play a key role in tumorigenesis. MUC15 is a membrane-bound mucin and the MUC15 messenger RNA (mRNA) has been detected in various organs. However, its role in tumor malignancy is still unclear. This study was to investigate the MUC15 expression in colorectal tumors and the role of MUC15 in colon cancer cells. We found that the mRNA expression of MUC15 was significantly higher in 70.8% (51/72) of colorectal tumors compared with their normal counterparts by real-time reverse transcription-polymerase chain reaction. Immunohistochemistry showed that MUC15 expression was increased in 82.6% (43/52) of colorectal tumors. MUC15 overexpression in HCT116 cells enhanced cell proliferation, cell-extracellular matrix adhesion, colony-forming ability and invasion. Furthermore, these effects were significantly reversed by knockdown of MUC15 with short-hairpin RNA. In nude mice models, MUC15 overexpression significantly (P < 0.01) enhanced tumor growth. In addition, treatment of PD98059 significantly (P < 0.01) inhibited MUC15-enhanced invasion, suggesting that the invasion induced by MUC15 in HCT116 cells was primarily mediated through activation of extracellular signal-regulated kinase 1/2. In conclusion, these results suggest that MUC15 is upregulated in colorectal tumors and its expression enhances the oncogenic potential of colon cancer cells.

Randomized trial of oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of spontaneous preterm labor in Taiwanese women.

BACKGROUND/PURPOSE: Management of preterm labor involves the use of tocolytic drugs to inhibit preterm uterine contractions. This study compared the efficacy and safety of intravenous administration of atosiban and ritodrine in the treatment of spontaneous preterm labor. METHODS: A randomized study was conducted in pregnant women of Chinese origin in Taiwan with threatened preterm delivery. Patients were randomized to receive either atosiban (n = 23) or ritodrine (n = 22). Tocolytic efficacy of the drug was assessed as the proportion of women who did not deliver and did not need alternative tocolytic treatment at 7 days after therapy initiation. Safety of the drugs was assessed as the number of adverse events or neonatal morbidity. RESULTS: The number of women who did not deliver and did not require alternative tocolytic therapy at 7 days was similar between the atosiban and ritodrine groups. There were no serious adverse events, but maternal cardiovascular adverse events, particularly tachycardia, occurred significantly more in women treated with ritodrine (0% atosiban vs. 18.18% ritodrine, p < 0.05). There was no difference in neonatal or infant outcome between the two drugs. CONCLUSION: The present study showed similar effectiveness between atosiban and ritodrine, while tachycardia occurred more frequently in women treated with ritodrine. These results indicate that atosiban is an effective tocolytic drug without the conventional cardiovascular side effects often seen with beta-agonist treatment.

Decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers.

BACKGROUND: Maternal anti-viral treatment prevents mother-to-infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear. AIMS: To investigate the effect of maternal anti-viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children. METHODS: Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months. RESULTS: The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10  IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10  IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P < 0.0001) and HBsAg seropositivity at 6 months (1.74% vs 11.83%, P = 0.003) and 12 months (1.74% vs 10.75%, P = 0.007). In a first multivariate analysis, maternal HBV DNA level at delivery (odds ratio = 1.70, P = 0.0172) and neonatal HBsAg positivity (odds ratio = 19.37, P < 0.0001) were significantly associated with children's chronic HBV infection. In a second model, neonatal HBV DNA positivity was a strong independent influence variable (odds ratio = 61.89, P = 0.0002). CONCLUSIONS: Maternal tenofovir therapy decreased maternal viral load and neonatal viremia. Positive neonatal HBV DNA was highly correlated with chronic HBV infection in children. Clinical Trial Identifier: NCT01312012.

Vascularity change and tumor response to neoadjuvant chemotherapy for advanced breast cancer.

For advanced breast cancer with severe local disease (ABC) (stage III/IV), neoadjuvant chemotherapy improves local control and surgical outcome. However, about approximately 20 to 30% of advanced cancers show either no or poor response to chemotherapy. To prevent unnecessary treatment, a capability of predicting clinical response to neoadjuvant chemotherapy of ABC is highly desirable. Vascularity index (VI) of breast cancers was derived from the quantification results in 30 ABC patients by using power Doppler sonography. Power Doppler sonography evaluation was performed every one to two weeks during chemotherapy. The overall response rate for 30 advanced patients tested was 70%, when 50% or more reduction in tumor size was the objective clinical response. Chemotherapy response was unrelated to the original tumor size (p = 0.563) or chemotherapy agents used (p = 0.657). The median VI for all 30 patients was 4.99%. The response rates for hypervascular tumors vs. hypovascular tumors, based on initial median value, were 86.7% and 53.3%, respectively (p = 0.109). The average VIs in responders and nonresponders were 7.67 +/- 4.77% and 4.01 +/- 3.82% (p = 0.052). There was a tendency for responders who have a relatively high initial vascularity. The VI change in responder group shows a pattern of initial increasing in vascularity followed by decreasing in vascularity. All patients (17/17) with a VI increment of >5% during chemotherapy had good chemotherapy response, whereas in patients with a VI increment of <5%, the response rate was 30.8% (4/13) (p < 0.001). For patients with a peak VI of >10% during chemotherapy, the response rate was 94.1% (16/17). However, in patients with a peak VI of <10%, the response rate was 38.5% (5/13) (p = 0.001). This prediction was made mostly within one month (25.47 +/- 12.96 d for VI increments >5% and 25.44 +/- 12.41 d for VI increased to >10%). In the meantime, the differences in size reduction shown in B-mode sonography were insignificant between responders and nonresponders (patient group with VI increment >5%, p = 0.308; patient group with peak VI >10%, p = 0.396). In conclusion, we propose that VI as determined by using power Doppler sonography is a good and inexpensive clinical tool for monitoring vascularity changes during neoadjuvant chemotherapy in ABC patients. Two parameters--VI increment >5% and peak VI >10%--are potential early predictors for good responses to neoadjuvant chemotherapy within one month in patients with ABC.

Sexual dysfunction predicts depressive symptoms during the first 2 years postpartum.

BACKGROUND: The association between sexual function and depression has yet to be examined in a prospective cohort study with prolonged postpartum follow-up. AIM: We investigated whether sexual dysfunction predicted depressive symptoms during the 24-month postpartum period and examined the influence of obstetric factors. METHODS: This prospective 2-year cohort study with repeated measures included 196 participants who were recruited in a medical center in Taipei, Taiwan (2010-2011). Data on participants' personal characteristics, sexual function, and depression symptoms at 4-6 weeks and at 3, 6, 12, and 24 months postpartum were collected and then assessed using the Female Sexual Function Index and the Center for Epidemiologic Studies Depression Scale. RESULTS: After adjusting for time and covariates, women with sexual dysfunction had a 1.62-fold (95% confidence interval [CI]: 1.05-2.50-fold) higher estimated odds ratio (OR) for depressive symptoms during the entire 24 months after childbirth than did women without sexual dysfunction. Risk factors for depressive symptoms were a higher pain score (OR: 1.33, 95% CI: 1.13-1.57), a medical condition (OR: 1.65, 95% CI: 1.00-2.73), and severe perineal laceration (OR: 4.67, 95% CI: 1.37-15.92). Sexual satisfaction during the entire 24 months after childbirth (OR: 0.81, 95% CI: 0.70-0.95) and the highest personal income level (OR: 0.33, 95% CI: 0.11-0.99) were factors protecting against higher-scoring depressive symptoms. CONCLUSIONS: Our study provides robust evidence that sexual dysfunction and poor satisfaction, together with severe perineal laceration, greater pain, and a medical condition, predict depressive symptoms during the 24-month postpartum period.

Outcome for fetuses with prenatally detected congenital heart disease and cardiac arrhythmias in Taiwan.

BACKGROUND/PURPOSE: Outcome for fetuses with prenatally detected congenital heart disease (CHD) and/or cardiac arrhythmias is important for prenatal counseling and perinatal management; however, there exists little literature regarding the outcome for CHD diagnosed in utero in Taiwan. Therefore, we attempted to investigate the outcome for fetuses with CHD and/or cardiac arrhythmias diagnosed prenatally at a tertiary care medical center in Taiwan. METHODS: Between January 1995 and December 2000, 339 patients referred to the National Taiwan University Hospital for fetal echocardiography were included in this study. Medical records were reviewed retrospectively to determine the salient clinical characteristics for all fetuses. RESULTS: CHD was found in 103 fetuses. Gestational age at diagnosis ranged from 17 to 40 weeks; in 37 cases (35.9%) the diagnosis was made before 24 weeks. Mean gestational age at diagnosis was 27.8 weeks. Of the 103 cases, 15 fetuses (14.6%) had major extra cardiac malformations and 15 fetuses (14.6%) had chromosomal abnormalities (five had both) and 30 pregnancies (29.1%) were terminated. Of the remaining 73 pregnancies, three (4.1%) of the fetuses died in utero and 28 (38.4%) postnatally, with 42 (57.5%) surviving. The mortality rates were both 60% in cases with extracardiac or chromosomal anomalies. Arrhythmias were identified in 25, and two pregnancies involving hydrops fetalis were terminated. Of the remaining 23 continued pregnancies, two (8.7%) with long QT syndrome expired postnatally. CONCLUSION: Outcome for fetuses with prenatally detected CHD remains poor, with the prognosis negatively influenced by the presence of complex heart defects as well as extracardiac and chromosomal anomalies. However, prognosis is good for fetuses with cardiac arrhythmia, except with long QT syndrome or hydrops fetalis.

Proximal GATA-binding sites are essential for human HSD3B1 gene transcription in the placenta.

The enzyme 3ß-hydroxysteroid dehydrogenase/isomerase (3ß-HSD) is involved in the synthesis of active steroid hormones. Two human 3ß-HSD isoforms are expressed in a tissue-specific pattern. HSD3B1 (type I) expression is essential to produce progesterone for pregnancy maintenance. To understand the mechanisms of human HSD3B1 activation in the placenta, 2.2 kb of 5'-flanking sequence and 5'-deletions were fused to the luciferase reporter gene and transfected into human JEG-3 cells. The proximal -238/+337 sequence had the highest promoter activity. Two GATA elements were identified at -106/-99 and -52/-45. Mutations of either sites greatly reduced promoter activity in JEG-3 cells, demonstrating the importance of GATA sites. EMSA revealed the specific binding of GATA2 and GATA3 to the GATA sequences at -106/-99 and -52/-45. ChIP assays demonstrated the association of GATA2 but not GATA3 with the GATA-binding regions of the HSD3B1 promoter in JEG-3 cells. GATA2 knockdown significantly reduced HSD3B1 expression in JEG-3 cells; however, GATA3 knockdown increased HSD3B1 expression. Western blot analysis revealed high levels of GATA2 but not GATA3 in human placental tissues. This study identified GATA motifs as essential control elements for HSD3B1 transcription and GATA2 as a novel transcriptional regulator of HSD3B1 expression in the human placenta.

SEN virus infection in children in Taiwan: transmission route and role in blood transfusion and liver diseases.

BACKGROUND: SEN virus (SENV) is a newly discovered DNA virus. We conducted this study to evaluate potential modes of SENV transmission and the pathogenic effect of SENV on liver diseases in children. METHODS: Polymerase chain reaction was used to detect 2 SENV variant (SENV-D and SENV-H) DNA in sera from healthy individuals and diseased children. Nucleotide sequence of SENV was determined by direct sequencing. RESULTS: SENV infection was assessed in healthy individuals, including 50 newborns (sera collected from the umbilical cord), 24 infants, 46 preschool children (aged 1-6 years), 42 school children of an age before that of the first sexual experience (aged 7-12 years), 62 adolescents (13-18 years), 72 young adults (19-30 years) and 32 adults (>30 years). The prevalence of SENV-D and/or SENV-H (SENV-D/H) viremia in each group was 0%, 17%, 24%, 24%, 27%, 33% and 40%, respectively. The prevalence of SENV-D/H viremia in 18 children with non-A to E hepatitis, 64 thalassemic children, 80 children transfused during cardiac surgery, 30 children with chronic hepatitis B, 9 children with chronic hepatitis C and 32 infants with biliary atresia was 11%, 61%, 80%, 83%, 67% and 50%, respectively. SENV was found more frequently in all patient groups than in 174 age-matched controls (P < 0.01), with the exception of non-A to E hepatitis (11% versus 24% in the control group; P = 0.27). In 2 infants with proven intrauterine hepatitis B viral infection, identical SENV-D nucleotide sequence existed in both the maternal and neonate serum. Elevated alanine aminotransferase concentrations were rarely observed in children who acquired isolated SENV viremia because of transfusion for surgery. Infection with SENV in children with chronic hepatitis C virus or hepatitis B viral infection was not associated with higher peak alanine aminotransferase values. CONCLUSION: SENV is transmitted mainly via nonparenteral daily contact and frequently occurs early in life. Transfusion can significantly increase the rate of SENV viremia. SENV does not appear to cause hepatitis in children.

Effect of availability of a parturient-elective regional labor pain relief service on the mode of delivery.

BACKGROUND/PURPOSE: Regional analgesia for labor pain relief is effective and widely used. This study evaluated the controversial association between mode of operative delivery and patient-elective labor regional analgesia. METHODS: We retrospectively compared the rates of instrumental vaginal and cesarean deliveries in parturients before the introduction, in the first 15 months after, and in the subsequent 36 months after the implementation of an elective labor regional analgesia service. A total of 9779 low-risk singleton cephalic pregnancies above 36 weeks of gestation were included. The maternal and fetal outcomes for parturients before the service was implemented and in those with or without pain relief service in the two postimplementation periods were analyzed. Multivariate logistic regression analyses were used to investigate the effects of maternal age, gestational weeks and newborn weight, in addition to regional analgesia, on the mode of delivery in nulliparous women. RESULTS: After adjusting for maternal age, gestational weeks, and newborn weight, no significant association was found between regional analgesia and cesarean delivery in nulliparas. Further, this lack of association was not affected by the receipt of regional analgesia in the early period of program implementation or in the period after staff had become familiar with the service. A higher rate of instrumental vaginal delivery was noted in nulliparas given regional analgesia. CONCLUSION: Regional analgesia for pain relief increased the likelihood of instrumental vaginal delivery, but did not increase the likelihood of cesarean delivery.

Relationships between perineal pain and postpartum depressive symptoms: A prospective cohort study.

BACKGROUND: The relationship between concurrent or previous postnatal pain and depressive symptoms remains controversial. To the best of our knowledge, no previous study has used validated measures and multiple scales to evaluate perineal pain, or examined its relationship with depressive symptoms during the postpartum period. OBJECTIVES: We investigated the association between pain and previous postnatal pain with depression during the 6-month postpartum period, and the influence of previous postnatal depressive symptoms. DESIGN: A prospective cohort study design was used. SETTING: Maternity unit of a medical center. PARTICIPANTS: This study included 432 participants; data regarding demographic characteristics, perineal pain, and any pain and depression during the 6-month postpartum period were collected. METHODS: Pain and depressive symptoms were measured using the Short Form-McGill Pain Questionnaire and Center for Epidemiologic Studies Depression Scale, respectively. A generalized estimating equation was used to examine factors associated with postpartum depression. RESULTS: After adjusting for covariates, women who had perineal pain at 4-6 weeks postpartum showed an increased risk for depression at 4-6 weeks (risk ratio [RR]: 1.9, 95% confidence limits [CL]: 1.2, 3.2) and 6 months (RR: 1.9, 95% CL: 1.1, 3.3) compared to those with no perineal pain. Perineal pain severity, 4-6 weeks postpartum, also predicted depressive symptoms at 6 months postpartum (ß=0.63, p=0.02). Any pain intensity score at 3-5 days postpartum predicted depression at 3 months (ß=0.01, p=0.04). Women with high depression scores at 3-5 days had a two- or three-fold higher risk for depression at 4-6 weeks and 3 and 6 months, respectively, compared to those with low depression scores (RR: 3.5, 95% CL: 2.2, 5.4; RR: 2.2, 95% CL: 1.3, 3.4; and RR: 2.8, 95% CL: 1.7, 4.8, respectively). CONCLUSIONS: Our study provides robust evidence that perineal pain 4-6 weeks postpartum is associated with depressive symptoms 4-6 weeks and 6 months postpartum; pain at 3-5 days postpartum predicts depressive symptoms at 3 months postpartum; and previous postnatal depressive symptoms, particularly depressive symptoms 3-5 days postpartum, predict depressive symptoms during the 6-month postpartum period.

Temporary balloon occlusion of the common iliac artery: new approach to bleeding control during cesarean hysterectomy for placenta percreta.

A case of placenta percreta was referred at 31 weeks' gestation. We performed a cesarean hysterectomy preceded by placement of occlusive balloon catheters at bilateral common iliac arteries at 34 weeks' gestation. This simple and safe technique provides satisfactory efficacy for control of profuse bleeding during operation, with blood loss estimated at 800 mL.