Birth outcomes following pelvic ring injury: A retrospective study.

OBJECTIVE: To report obstetric outcomes in pregnant women with previous pelvic ring injury (PRI) and investigate the correlation between residual pelvic deformity and the mode of delivery. DESIGN: Retrospective cohort study. SETTING: Single medical centre in Taiwan. POPULATION: Forty-one women with PRI histories from 2000 to 2021 who subsequently underwent pregnancy and delivery. METHODS: All patients had complete PRI treatment and radiological follow up for at least 1 year. The demographic data, radiological outcomes after PRI and obstetric outcomes were collected to investigate the potential factors of delivery modes using non-parametric approaches and logistic regression. Caesarean section (CS) rates among different subgroups were reported. MAIN OUTCOME MEASURES: Comparisons of demographic data and radiological outcomes (Matta/Tornetta criteria and Lefaivre criteria) after PRI among patients who had subsequent pregnancy and underwent vaginal deliveries (VD) or CS. RESULTS: There were 14 VD and 27 CS in 41 patients. Nine patients underwent CS because of their PRI history, 12 patients underwent CS for other obstetric indications and 20 underwent trial of labour. Based on the logistic regression model, retained trans-iliosacral implants did not significantly increase the risk of CS (odds ratio [OR] 1.20; 95% CI 0.17-8.38). Higher pelvic asymmetry value by Lefaivre criteria was a potential risk factor for CS after previous PRI (OR 1.52; 95% CI 1.043-2.213). CONCLUSIONS: VD is possible after PRI. Retained trans-iliosacral implants do not affect the delivery outcome. Residual pelvic asymmetry after PRI by Lefaivre criteria is a potential risk factor for CS.

Risk factors associated with periodontal disease and its impact on quality of life among pregnant women.

BACKGROUND: Periodontal disease during pregnancy affects maternal oral health and increases the risk of adverse pregnancy outcomes. However, studies on the risk factors for periodontal disease and its impact on oral health-related quality of life in pregnant women in Taiwan are lacking. This present study aimed to identify the risk factors associated with periodontal disease during pregnancy and examine the relationship of periodontal disease with oral health-related quality of life among pregnant women. METHODS: This study was conducted in a large medical centre in northern Taiwan. Eighty-four participants completed a periodontal examination by dentists as well as structured questionnaires, including the Oral Health Impact Profile-14, demographics, obstetric history, dietary habits, and oral hygiene behaviours. Multivariate logistic regression was used to determine the risk factors associated with periodontal disease and a t-test was used to compare the difference in oral health-related quality of life between pregnant women with and without periodontal disease. RESULTS: Fifty participants (59.5%) had periodontal diseases. Risk factors for periodontal disease included eating out for lunch, consuming beverages, brushing less than three times per day, and not receiving regular professional dental cleanings. The oral health-related quality of life was significantly poorer in pregnant women with periodontal disease than in those without. CONCLUSIONS: The risk factors for periodontal disease, including eating out for lunch, drinking beverages, brushing teeth less, and not regular dental cleaning, provide convincing evidence for pregnant women to maintain good oral hygiene to prevent periodontal disease and improve oral health-related quality of life.

Pregnancy can cause poor mouth health. Expectant mothers with gum disease might face problems such as low birth weight and premature birth. This study found that certain factors can worsen gum disease during pregnancy. These include eating out for lunch, drinking sugary or acidic drinks, brushing their teeth less than three daily, and skipping regular teeth cleaning by a dentist. Pregnant women with gum disease also reported a lower quality of life related to oral health compared to those without it. Healthcare providers should educate pregnant women about oral health maintenance. Emphasize the importance of professional dental cleanings every three months, frequent tooth brushing, avoiding sugary and acidic drinks, and reducing eating out for lunch. Future research should explore additional ways to support pregnant women in this regard.

Absence of chronicity in infants born to immunized mothers with occult HBV infection in Taiwan.

BACKGROUND & AIMS: In the Taiwanese population born in the universal vaccination era, HBsAg carrier rates have fallen below 2%, while approximately 5% develop occult hepatitis B infection (OBI). However, the potential for transmission from mothers with OBI to their infants has not been well studied. We aimed to investigate whether mothers with OBI could transmit HBV to their babies. METHODS: A total of 253 pregnant women who were born after July 1986 and had been fully vaccinated against HBV during infancy were recruited from a tertiary hospital in Northern Taiwan. HBV serology and DNA levels were determined. Babies born to mothers with OBI were followed-up until 1 year of age. The surface genes were sequenced. RESULTS: HBV infection was documented in 18 vaccinated mothers, 2 of whom were HBsAg-reactive (0.79 %). Seventeen were positive for HBV DNA, among whom 16 (6.32%) presented with OBI with a median DNA level of 145 IU/ml (interquartile range: 37.8-657.3 IU/ml). Eleven babies born to 10 mothers with OBI were recruited. Three babies were HBsAg-reactive, and 2 were positive for HBV DNA (17.0 and 212.0 IU/ml). Seven mothers with OBI carried multiple surface gene variants. Two transiently infected babies harbored variants originating from their mother's HBV quasi-species. All infants received complete hepatitis B vaccines. At 12 months of age, none of the babies were positive for HBsAg or HBV DNA. CONCLUSIONS: It was possible for mothers with OBI to transmit HBV to their babies, who consequently harbored surface gene variants originating from their mothers' minor variants. Viremia was cleared 1 year after completing the hepatitis B vaccination series. LAY SUMMARY: Since initiating the hepatitis B vaccination program in Taiwan, the rate of young individuals (i.e. born after 1986) carrying the HBV surface antigen has fallen below 2%, although around 5% of vaccinated individuals develop occult HBV infections. Herein, we show that pregnant mothers with occult HBV infections can transmit HBV to their offspring. However, no infant had sustained infection at 1 year of age having completed a full HBV vaccination series.

Incidence, prognosis, and perinatal outcomes of and risk factors for severe twin-twin transfusion syndrome with right ventricular outflow tract obstruction in the recipient twin after fetoscopic laser photocoagulation.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is the most frequently encountered congenital heart disease in patients with twin -twin transfusion syndrome (TTTS) and is especially prevalent in the recipient twin. In this retrospective study, we evaluated the incidence, prognosis, postnatal management, and perinatal outcomes of and risk factors for RVOTO in the recipient twin in severe TTTS cases which diagnosed before 26 weeks after fetoscopic laser photocoagulation (FLP) at a single center in Taiwan. METHODS: RVOTO was diagnosed using fetal or postnatal echocardiography. The fetal outcomes evaluated were perinatal survival rate, neonatal brain image anomalies rate, gestational age at delivery, and birth weight. RESULTS: Total 187 severe TTTS cases were included; 14 (7.49%) had a recipient twin with RVOTO (12 cases of pulmonary stenosis and 2 of pulmonary atresia). Of these 14 cases, 3 (21.4%) demonstrated improvements in outflow obstruction after FLP, and 11 (78.6%) resulted in perinatal survival. Of the 11 survivors, 5 (45.5%) received transcatheter balloon valvuloplasty to alleviate the RVOTO. The perinatal survival rate, gestational age at delivery, neonatal brain image anomaly rate, and birth weights did not significantly differ between the groups in which the recipient twin had versus did not have RVOTO. Generally, the recipient twin had RVOTO received FLP at a younger gestational age (in weeks; 19.3 ± 2.4 vs. 20.7 ± 2.6, p = 0.048) and had a higher percentage of cases at Quintero stage IV (50.0% vs. 12.1%, p < 0.001) than those in which the recipient twin did not have with RVOTO. Using logistic regression, we discovered that FLP at a younger gestational age (p = 0.046, odds ratio = 0.779) and TTTS at Quintero stage IV (p = 0.001, odds ratio = 7.206) were risk factors for the recipient twin developing RVOTO after FLP in severe TTTS cases. CONCLUSIONS: The post-FLP perinatal outcomes of cases of severe TTTS in which the recipient twin had versus did not have RVOTO were comparable in this study, which may have been due to the similar gestational ages at delivery and strong influence of high Quintero stages (stages III and IV).

The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study.

BACKGROUND: The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019. METHODS: The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website. RESULTS: This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively. CONCLUSION: During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

Placental glucose transporter 1 and 3 gene expression in Monochorionic twin pregnancies with selective fetal growth restriction.

BACKGROUND: In monochorionic twin (MC) gestations with selective fetal growth restriction (FGR), the discordant fetal growth usually is due to unequal placental sharing. Glucose, which is essential for oxidative metabolism in the growing placenta and fetus, is transferred from maternal blood by facilitated carrier-mediated diffusion via glucose transporters (GLUTs). How the GLUTs expression varies in the two placenta territories manifests discordant perfusion in MC twin pregnancy with selective FGR is unknown. This study evaluates the human placental GLUT1 and GLUT3 gene expression in MC twin gestations with selective FGR. METHODS: MC twin pregnancy with selective FGR was defined as the presence of inter-twin birth weight discordance of > 25% and the smaller twin with a birth weight less than the 10th percentile in third trimester. Fetal umbilical artery Doppler was checked within 1 week before delivery in the two fetuses. An abnormal umbilical artery Doppler was defined as persistently absent or reverse end-diastolic flow (UA-AREDF). GLUT1, GLUT3 and HIF-1α gene expression were assayed in each twin's placental territories. The inter-twin placental gene expression ratio was calculated as the placenta GLUTs or HIF-1α expression level of the selective FGR twin divided by expression level of the appropriate-for-gestational-age (AGA) cotwin. Higher gene expression ratio means elevated gene expression in the selective FGR twin's placenta territory compared to AGA twin's placenta territory. RESULTS: 15 MC twin gestations with selective FGR including nine with normal (group 1) and six with abnormal selective FGR twin UA Doppler (group 2) were included into this study. The GLUT3 and HIF-1α gene expression are significantly elevated in selective FGR twin's placenta territory in group 2 twin pregnancies (mean gene expression ratio as 2.23 and 1.65, p values as 0.015 and 0.045, respectively), but not in in group 1 twin pregnancies. CONCLUSION: The upregulation of placental GLUT3 gene expression in selective FGR fetus with abnormal UA Doppler may be due to hypo-perfusion which is mediated by up -regulation of HIF-1α gene expression.

Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome.

OBJECTIVE: DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. METHODS: This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. RESULTS: Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57-100.00%) and 99.92% (95% CI 99.83-99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14-76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. DISCUSSION/CONCLUSION: NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

Predisposing factors and neonatal outcomes for twin-twin transfusion syndrome cases developing transient donor hydrops after fetoscopic laser coagulation: a case control study.

BACKGROUND: Transient donor hydrops (TDH) is defined as donor hydrops developed within days after laser therapy for twin-twin transfusion syndrome (TTTS) followed by resolution later. The purpose of this study was to evaluate the incidence, neonatal outcomes and predisposing factors of post laser therapy TDH in severe TTTS. METHODS: A total of 142 patients with severe TTTS who received laser therapy were included into this study. The pre-operative characteristics and neonatal outcomes were compared between TTTS with and without post laser therapy TDH. All live neonates received cranial ultrasound examination after delivery, mild cerebral injury was defined as exhibiting at least one of the following: intraventricular hemorrhage (IVH) grade I and II, lenticulostriate vasculopathy and subependymal pseudocysts; severe cerebral injury comprised at least one among the following: IVH grade III or grade IV, cystic periventriculoleukomalacia (PVL) grade II or more, porencephalic cysts, and ventricular dilatation. Fetal survival was defined as living more than 30 days after delivery.

Effects and outcomes of septostomy in twin-to-twin transfusion syndrome after fetoscopic laser therapy.

BACKGROUND: To evaluate the incidence and outcomes of septostomy in twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser therapy. METHODS: A retrospective analysis of TTTS postlaser septostomy between 2005 and 2018 was performed. Postlaser septostomy was diagnosed using both (1) a free-floating intertwin membrane flap visible on ultrasound examination and (2) the rapid equalization of amniotic fluid maximum vertical pocket in the donor and recipient amniotic sacs observed after laser therapy. Perinatal survival, neonatal brain image anomaly, gestational age at operation and birth, incidence of premature rupture of membranes (PROM) within 3 weeks after operation, pseudoamniotic band syndrome, and cord entanglement were evaluated. RESULTS: In the 159 TTTS cases included, 12 had postlaser septostomy. Relative to the group without septostomy, the septostomy group had a lower total fetal survival rate (54.2% vs 73.6%, p = 0.041), an earlier mean gestational age at delivery (27.8 vs 34.4 weeks, p = 0.009), a higher risk of PROMs within 3 weeks after operation (33.3% vs 5.4%, p = 0.004), a higher cord entanglement rate (16.7% vs 0%, p = 0.005), and a higher brain image anomaly rate (23.0% [3/13] vs 5.0% [11/218], p = 0.035). After considering the severe Quintero stages (stage III and IV), postlaser septostomy was the only variable [p = 0.003, odds ratio = 5.1] to predict neonatal brain image anomaly. Postlaser septostomy combined with severe Quintero stages could predict PROMs within 3 weeks after laser therapy [p = 0.001, odds ratio = 14.1 and p = 0.03, odds ratio = 5.4, respectively] and delivery before the gestational age of 28 weeks [p = 0.017, odds ratio = 4.5 and p = 0.034, odds ratio = 2.3, respectively]. The risk of pseudoamniotic band syndrome was not increased by postlaser septostomy in this case series. CONCLUSIONS: Postlaser septostomy in TTTS was associated with poorer fetal survival and more adverse perinatal outcomes even after considering severe Quintero stages before laser therapy. Efforts should be made to prevent septostomy during laser therapy, and septostomy as the primary method to treat TTTS is not advisable.

Numerical analysis of power dissipation requirement in magnetic hyperthermia problems.

Control of the therapeutic temperature is essential in performing magnetic fluid hyperthermia. Thus, reliable predictions of the power dissipation are required to determine the correct dosage of magnetic particles to be injected into the cancerous tissue prior to treatment. To meet this requirement, the present study evaluates the power dissipation requirement for two magnetic hyperthermia problems reported in the literature. There is a significant challenge for solving the bio-heat transfer model for concentric bi-layered solid spheres. Consequently, the present study employs a hybrid technique based on Laplace transformation and a modified discretization scheme to solve the considered hyperthermia problems. Analytical solutions are provided to demonstrate the validity of the proposed approach. The unreliability of the results presented in the literature is then demonstrated using the proposed numerical scheme. In general, the results presented in this study show that the power dissipation required to maintain an effective temperature range in the tumor domain is related to the rate of temperature rise, the tumor size, the blood perfusion rate, and the tissue properties. In particular, the power dissipation should be increased for the cooling effect of blood perfusion or a smaller tumor volume.

Population-based trends and risk factors of early- and late-onset preeclampsia in Taiwan 2001-2014.

BACKGROUND: Preeclampsia, a multisystem disorder in pregnancies complicates with maternal and fetal morbidity. Early- and late-onset preeclampsia, defined as preeclampsia developed before and after 34 weeks of gestation, respectively. The early-onset disease was less prevalent but associated with poorer outcomes. Moreover, the risk factors between early -and late- onset preeclampsia could be differed owing to the varied pathophysiology. In the study, we evaluated the incidences, trends, and risk factors of early- and late- onset preeclampsia in Taiwan. METHODS: This retrospective population-based cohort study included all ≧20 weeks singleton pregnancies resulting in live-born babies or stillbirths in Taiwan between January 1, 2001 and December 31, 2014 (n = 2,884,347). The data was collected electronically in Taiwanese Birth Register and National Health Insurance Research Database. The incidences and trends of early- and late-onset preeclampsia were assessed through Joinpoint analysis. Multivariate logistic regression was used to analyze the risk factors of both diseases. RESULTS: The age-adjusted overall preeclampsia rate was slightly increased from 1.1%(95%confidence interval [CI], 1.1-1.2) in 2001 to 1.3% (95%CI, 1.2-1.3) in 2012 with average annual percentage change (AAPC) 0.1%/year (95%CI, 0-0.2%). However, the incidence was remarkably increased from 1.3% (95%CI, 1.3-1.4) in 2012 to 1.7% (95%CI, 1.6-1.8) in 2014 with AAPC 1.3%/year (95%CI,0.3-2.5). Over the study period, the incidence trend in late-onset preeclampsia was steadily increasing from 0.7% (95%CI, 0.6-0.7) in 2001 to 0.9% (95%CI, 0.8-0.9) in 2014 with AAPC 0.2%/year (95%CI, 0.2-0.3) but in early-onset preeclampsia was predominantly increase from 0.5% (95%CI, 0.4-0.5) in 2012 to 0.8% (95%CI, 0.8-0.9) in 2014 with AAPC 2.3%/year (95%CI, 0.8-4.0). Advanced maternal age, primiparity, stroke, diabetes mellitus, chronic hypertension, and hyperthyroidism were risk factors of preeclampsia. Comparing early- and late-onset diseases, chronic hypertension (ratio of relative risk [RRR], 1.71; 95%CI, 1.55-1.88) and older age (RRR, 1.41; 95%CI 1.29-1.54) were more strongly associated with early-onset disease, whereas primiparity (RRR 0.71, 95%CI, 0.68-0.75) had stronger association with late-onset preeclampsia. CONCLUSIONS: The incidences of overall, and early- and late-onset preeclampsia were increasing in Taiwan from 2001 to 2014, predominantly for early-onset disease. Pregnant women with older age and chronic hypertension had significantly higher risk of early-onset preeclampsia.

Placental erythropoietin expression is upregulated in growth-restricted fetuses with abnormal umbilical artery Doppler findings: a case-control study of monochorionic twins.

BACKGROUND: We previously reported that fetal plasma erythropoietin (EPO) concentrations are significantly increased in growth-restricted fetuses with abnormal umbilical artery (UA) Doppler. During hypoxia in an ovine model, the primary site of fetal EPO synthesis was switched from the kidneys to the placenta. Therefore, we designed this study to evaluate human placental EPO gene expression and the correlation to fetal serum EPO concentration in growth-restricted fetuses in a monochorionic (MC) twin model. METHODS: In MC twin pairs, selective intrauterine growth restriction (sIUGR) was defined as the presence of (i) birth weight discordance of > 20% and (ii) a smaller twin with a birth weight less than the 10th percentile. Fetal UA and middle cerebral artery (MCA) Doppler were checked within 1 week before delivery. An abnormal UA Doppler was defined as persistently absent or reverse end-diastolic flow. Cerebroplacental ratio (CPR) was defined as MCA-pulsatility index (PI)/UA-PI. Fetal plasma EPO concentrations were measured in cord blood, and EPO gene expression was assayed in each twin's placental territory. The intertwin plasma EPO ratio was calculated as the cord plasma EPO level of the smaller (or sIUGR) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin, and the intertwin placental EPO gene expression ratio was calculated similarly. RESULTS: Twenty-six MC twins were analyzed, including normal twins (Group 1, n = 9), twins with sIUGR without UA Doppler abnormalities (Group 2, n = 9), and twins with sIUGR and UA Doppler abnormalities (Group 3, n = 8). The CPRs of smaller (sIUGR) fetuses were significantly decreased in Group 3 MC twins (p < 0.001), but not significantly different between Group 1 and Group 2. The highest fetal plasma EPO ratio and placental EPO gene expression ratio were identified in Group 3 MC twins (p < 0.001). The placental EPO gene expression ratios were significantly correlated with the fetal plasma EPO ratios (Pearson's correlation test, p = 0.004). CONCLUSION: This study provides evidence of increased placental EPO expression in MC twin fetuses with sIUGR and abnormal UA Doppler. Future studies are needed to confirm the similar role of placental EPO in severe IUGR singletons.

Maternal and neonatal outcomes of respiratory failure during pregnancy.

BACKGROUND: Obstetric patients comprise a limited portion of intensive care unit patients, but they often present with unfamiliar conditions and exhibit the potential for catastrophic deterioration. This study evaluated the maternal and neonatal outcomes of respiratory failure during pregnancy. METHODS: Information on 71 patients at >25 weeks gestation in the ICU with respiratory failure was recorded between 2009 and 2013. The characteristics and outcomes of mothers and fetuses were determined through a retrospective chart review and evaluated using Student's t test, chi-square test, and Fisher's exact test. RESULTS: The leading causes of respiratory failure were postpartum hemorrhage and severe preeclampsia in the obstetric causes group and pneumonia in the nonobstetric causes group during pregnancy and the peripartum period. The non-obstetric causes group exhibited a higher incidence of acute respiratory distress syndrome and renal replacement therapy as well as requiring more ventilator days. The patients in the obstetric causes group showed significant improvement after delivery in the partial pressure of arterial oxygen to the fraction of inspired oxygen and peak inspiratory pressure decrease. Both groups exhibited high incidences of neonatal respiratory distress syndrome. Neonatal complications resulting from meconium aspiration syndrome (MAS) and sepsis were more common in the non-obstetric causes group; however, neurological development impairment was more common in the obstetric causes group. CONCLUSION: Obstetric cause was associated with longer ventilator free days and fewer episodes of ARDS after delivery. Neonatal complications resulting from different etiologies of respiratory failure were found to differ.

Nonsynonymous variants in MYH9 and ABCA4 are the most frequent risk loci associated with nonsyndromic orofacial cleft in Taiwanese population.

BACKGROUND: Nonsyndromic orofacial cleft is a common birth defect with a complex etiology, including multiple genetic and environmental risk factors. Recent whole genome analyses suggested associations between nonsyndromic orofacial cleft and up to 18 genetic risk loci (ABCA4, BMP4, CRISPLD2, GSTT1, FGF8, FGFR2, FOXE1, IRF6, MAFB, MSX1, MTHFR, MYH9, PDGFC, PVRL1, SUMO1, TGFA, TGFB3, and VAX1), each of which confers a different relative risk in different populations. We evaluate the nonsynonymous variants in these 18 genetic risk loci in nonsyndromic orofacial clefts and normal controls to clarify the specific variants in Taiwanese population. METHODS: We evaluated these 18 genetic risk loci in 103 cases of nonsyndromic orofacial clefts and 100 normal controls using a next-generation sequencing (NGS) customized panel and manipulated a whole-exon targeted-sequencing study based on the NGS system of an Ion Torrent Personal Genome Machine (IT-PGM). IT-PGM data processing, including alignment with the human genome build 19 reference genome (hg19), base calling, trimming of barcoded adapter sequences, and filtering of poor signal reads, was performed using the IT platform-specific pipeline software Torrent Suite, version 4.2, with the plug-in "variant caller" program. Further advanced annotation was facilitated by uploading the exported VCF file from Variant Caller to the commercial software package Ion Reporter; the free online annotation software Vanno and Mutation Taster. Benign or tolerated amino acid changes were excluded after analysis using sorting intolerant from tolerant and polymorphism phenotyping. Sanger sequencing was used to validate the significant variants identified by NGS. Furthermore, each variant was confirmed in asymptomatic controls using the Sequenom MassARRAY (San Diego, CA, USA). RESULTS: We identified totally 22 types of nonsynonymous variants specific in nonsyndromic orofacial clefts, including 19 single nucleotide variants, 2 deletions, and 1 duplication in 10 studied genes(ABCA4, MYH9, MTHFR, CRISPLD2, FGF8, PVRL1, FOXE1, VAX1, FGFR2, and IRF6). Nonsynonymous variants in MYH9 and ABCA4, which were detected in 6 and 5 individuals, respectively, were identified to be the most frequent risk loci in nonsyndromic orofacial clefts in the Taiwanese population. CONCLUSIONS: Nonsynonymous variants in MYH9 and ABCA4 were identified to be the most frequent risk loci in nonsyndromic orofacial clefts in the Taiwanese population. These findings in our study have provided additional information regarding specific variants associated with nonsyndromic orofacial clefts in different population and demonstrate the power of our customized NGS panel, which is clinically useful for the simultaneous detection of multiple genes associated with nonsyndromic orofacial clefts.

Sheep CD34+ amniotic fluid cells have hematopoietic potential and engraft after autologous in utero transplantation.

Unmatched allogeneic in utero stem cell transplantation (IUSCT) produces poor engraftment unless the fetus has congenital immunodeficiency, probably because of maternal and fetal immune responses to injected cells. We studied the functional hematopoietic potential of transduced green fluorescent protein (GFP+) sheep amniotic fluid (AF) stem cells, before and after autologous IUSCT. CD34+ cells were selected from first trimester sheep AF, transduced overnight, and injected intravenously into NOD-SCID-gamma (NSG) mice. At 3 months, primary recipient bone marrow (BM) was injected into secondary NSG recipients. GFP+ cells were detected in the hematopoietic organs and peripheral blood of primary and secondary recipients at 3 months. Autologous IUSCT (transduced GFP+CD34+AF) was performed in fetal sheep. Six months postnatally, lamb BM was injected into secondary NSG recipients. GFP+ cells were detected in the peripheral blood of primary and secondary recipients. This confirms the hematopoietic potential of AF stem cells supporting the concept of autologous IUSCT to treat congenital hematopoietic disease.

Low-molecular-weight-heparin can benefit women with recurrent pregnancy loss and sole protein S deficiency: a historical control cohort study from Taiwan.

BACKGROUND: Heritable thrombophilias are assumed important etiologies for recurrent pregnancy loss. Unlike in the Caucasian populations, protein S and protein C deficiencies, instead of Factor V Lieden and Prothrombin mutations, are relatively common in the Han Chinese population. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent pregnancy loss and documented protein S deficiency. METHODS: During 2011-2016, 68 women with recurrent pregnancy loss (RPL) and protein S deficiency (both the free antigen and function of protein S were reduced) were initially enrolled. All the women must have experienced at least three recurrent miscarriages. After excluding those carrying balanced translocation, medical condition such as diabetes mellitus, chronic hypertension, and autoimmune disorders (including systemic lupus erythematosus and anti-phospholipid syndrome), coexisting thrombophilias other than persistent protein S deficiency (including transient low protein S level, protein C deficiency, and antithrombin III), only 51 women with RPL and sole protein S deficiency were enrolled. Initially they were prescribed low dose Aspirin (ASA: 100 mg/day) and unfortunately there were still 39 women ended up again with early pregnancy loss (12 livebirths were achieved though). Low-molecular-weight-heparin (LMWH) was given for the 39 women in a dose of 1 mg/Kg every 12 h from the day when the next clinical pregnancy was confirmed to the timing at least 24 h before delivery. The perinatal outcomes were assessed. RESULTS: Of 50 treatment subjects performed for the 39 women (i.e. 11 women enrolled twice for two pregnancies), 46 singletons and one twin achieved livebirths. The successful live-birth rate in the whole series was 94 % (47/50). Nineteen livebirths delivered vaginally whereas 28 delivered by cesarean section. The cesarean delivery rate is thus 59.57 %. Emergent deliveries occurred in 3 but no postpartum hemorrhage had been noted. CONCLUSIONS: Our pilot study in Taiwan, an East Asian population, indicated anti-coagulation therapy is of benefit to women with recurrent pregnancy loss who had documented sole protein S deficiency. TRIAL REGISTRATION: ISRCTN64574169. Retrospectively registered 29 Jun 2016.

Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia.

Characterization of Human Pregnancy Specific Glycoprotein (PSG) Gene Copy Number Variations in Pre-eclampsia Patients.

Pre-eclampsia is a pregnancy-specific hypertensive disorder that affects 2-8 % of pregnancies. This disorder can lead to seizure, multi-organ failure and maternal death. The best approach to prevent pre-eclampsia-associated adverse outcomes is to be able to prevent pre-eclampsia as early as possible. Unfortunately, current diagnostic methods are ineffective at predicting the risk of pre-eclampsia during early pregnancy. In humans, low levels of a group of placenta-derived Pregnancy Specific Glycoproteins (PSGs) have been associated with intrauterine growth retardation and pre-eclampsia and there is a significant enrichment of cases with deletions in the PSG gene locus in pre-eclampsia patients. Based on these observations, we hypothesize that genomic variations at human PSG locus of maternal and/or fetal genomes may confer increased risks of pre-eclampsia. To test this hypothesis, we have recruited 90 normal control and 30 pre-eclamptic women for the analysis of fetal PSG copy number variations (CNVs).The identification of novel PSG CNV-disease relationships will provide not only a better understanding of the pathology of pre-eclampsia but also a novel opportunity to identify patients with a high risk of developing early-onset pre-eclampsia, which has a five- to tenfold higher risk of life-threatening maternal complications and fetal demise as compared to late-onset pre-eclampsia patients.

Efficiency of Screening for the Recurrence of Antenatal Group B Streptococcus Colonization in a Subsequent Pregnancy: A Systematic Review and Meta-analysis with Independent Patient Data.

OBJECTIVE: The objective of this study was to evaluate the risk of recurrent group B streptococcus (GBS) colonization in a subsequent pregnancy and to assess clinical characteristics that influence this risk. STUDY DESIGN: A systematic review and meta-analysis was performed. Databases were searched from inception through June 2015 using PubMed, Embase, Scopus, Central, and ClinicalTrials.gov. Studies were eligible if they assessed antenatal GBS colonization in two successive pregnancies. The quality of included studies was evaluated. Independent patient data was requested from the authors of the included trials. Unadjusted odds ratios (OR) were pooled using the Mantel-Haenszel fixed effect model. RESULTS: In the five studies identified, two studies lacked a nonexposed cohort. GBS colonization in the index pregnancy was associated with a higher risk of recurrence of GBS colonization in a subsequent pregnancy (three studies: 50.2 compared with 14.1%; pooled fixed effects OR, 6.05; 95% confidence interval [CI], 4.84-7.55). When heavy colonization with GBS was compared with colonization by vaginal culture only, an increased risk of recurrence was shown (four studies: 52.0 compared with 45.1%, pooled fixed effects OR, 1.54; 95% CI, 1.02-2.31). CONCLUSION: Women colonized with GBS are at significantly higher odds for recurrent colonization in a subsequent pregnancy when compared with women who were not colonized in an index pregnancy. If the individual is considered heavily colonized with GBS, there appears to be an association with an increased risk compared with conventional culture. Subgroup analysis of the variables time interval ≤ 12 months between subsequent pregnancies, body mass index ≥ 30 kg/m(2), race, ethnicity, and primiparous in the subsequent pregnancy showed no effect.