Perinatal lethal form Gaucher disease with compound heterozygosity of single nucleotide variants and copy number variations presenting as nonimmune hydrops fetalis and cerebellar hypoplasia: A case report.

OBJECTIVE: To present the ultrasound imaging and genetic diagnosis of a fetus with prenatal lethal form of Gaucher disease. CASE REPORT: A 37-year-old primiparous woman was pregnant at her 23 weeks of gestation and the prenatal fetal ultrasound revealed hydrops fetalis, cerebellum hypoplasia, and fetal immobility. The pregnancy was terminated due to major fetal anomaly, and whole exome sequencing (WES) analysis of fetal tissue and parental blood unveiled a pathogenic variant in exon 10 of the GBA gene (NM_001005741.3: c.1265T > G: p.L422R) originating from the mother. Additionally, a novel CNV (chr1: 155204785-155205635 deletion, 0.85 kb) spanning exon 10-12 in the GBA gene was identified from the father. This compound heterozygosity confirmed the diagnosis of prenatal lethal form of Gaucher disease and was informative for genetic counseling. CONCLUSION: WES is a powerful tool to detect pathogenic variants among fetuses with nonimmune hydrops fetalis and complex abnormality from prenatal ultrasound. Compound heterozygosity consisted of single nucleotide variants (SNV) and copy number variations (CNVs) may lead rare inherited metabolic disorders including prenatal lethal form of Gaucher disease.

Metabolomic profiling of maternal plasma identifies inverse associations of acetate and urea with anti-SARS-CoV-2 antibody titers following COVID-19 vaccination during pregnancy.

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. KEY MESSAGES : Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers.

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.

Effect of Gestational Age at Fetoscopic Laser Photocoagulation on Perinatal Outcomes for Patients with Twin-Twin Transfusion Syndrome.

PURPOSE: The aim of this study was to evaluate the effect of gestational age (GA) at the time of fetoscopic laser photocoagulation (FLP) for severe twin-twin transfusion syndrome (TTTS) on perinatal outcomes in a single center in Taiwan. MATERIALS AND METHODS: Severe TTTS was defined as a diagnosis of TTTS before a GA of 26 weeks. Consecutive cases of severe TTTS treated at our hospital with FLP between October 2005 and September 2022 were included. The evaluated perinatal outcomes were preterm premature rupture of membranes (PPROM) within 21 days of FLP, survival 28 days after delivery, GA at delivery, and neonatal brain sonographic imaging findings within 1 month of delivery. RESULTS: We included 197 severe TTTS cases; the mean GA at the time of FLP was 20.6 weeks. After the cases were divided into cases of FLP at early (below 20 weeks) and late GAs (more than 20 weeks), the early-GA group was discovered to be associated with a deeper maximum vertical pocket in the recipient twin, a higher rate of PPROM development within 21 days of FLP, and lower rates of survival of one or both twins. In the cases of stage I TTTS, the rate of PPROM within 21 days of FLP was higher in the group that underwent FLP at an early GA than in the group that underwent FLP at a late GA (50% (3/6) vs. 0% (0/24), respectively, p = 0.005). Logistic regression analysis revealed that the GA at the time of FLP and the cervical length before FLP is implemented are significantly associated with the survival of one twin and the incidence of PPROM development within 21 days of FLP. The GA at the time of FLP, the cervical length before FLP, and TTTS being stage III TTTS were associated with the survival of both twins after FLP. Neonatal brain image anomalies were associated with GA at delivery. CONCLUSIONS: FLP being performed at an earlier GA is a risk factor for lower fetal survival and PPROM development within 21 days of FLP in cases of severe TTTS. Delaying FLP for cases involving stage I TTTS diagnosed at an early GA without risk factors, such as maternal symptoms, cardiac overload in the recipient twin, or a short cervical length, may be considered, but whether delaying FLP would improve surgical outcomes and, if so, how long the delay should be may need further trials to answer.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome type 1 with an 814 kb Xq26.2 deletion with the initial presentation of a thick nuchal fold.

OBJECTIVE: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by overgrowth and multiple anomalies. Most clinical diagnoses of SGBS1 are made postnatally. We present the case of a pregnant woman in whom the fetus presented with a thick nuchal fold 5.6 mm at 15 weeks of gestation, leading to the prenatal diagnosis of SGBS1 with Xq26.2 (133408101-134221889) deletion. CASE REPORT: We report the case of a 34-year-old pregnant woman with the initial presentation of fetal thick nuchal fold 5.6 mm at 15 weeks of gestation. Amniocentesis of the fetal karyotype revealed a normal 46, XY, and single nucleotide polymorphism array showed Xq26.2 (133408101-134221889) deletion. Prenatal ultrasound at 21 weeks of gestation revealed a thick nuchal fold, hepatomegaly, nephromegaly, congenital diaphragmatic hernia, hypospadias, and polyhydramnios. Fetal magnetic resonance imaging revealed hepatomegaly, nephromegaly, congenital diaphragmatic hernia, and right lung hypoplasia. The woman had her pregnancy terminated at 24 weeks of gestation. The proband had a general appearance of low-set ears, hypertelorism, a large tongue, and hypospadias and some unique findings on autopsy, including hepatomegaly, right hiatal hernia, liver extensive extramedullary hematopoiesis, kidney marked congestion, and focal hemorrhage. DISCUSSION: The main prenatal ultrasound findings that alert clinical doctors about the possible diagnosis of SGBS1 included macrosomia, polyhydramnios, organomegaly, renal malformations, congenital diaphragmatic hernia, and cardiac anomalies. Our case underscores the importance of fetal karyotyping combined with single nucleotide polymorphism array when a thick nuchal fold is found. Genetic counseling is essential in SGBS1, and prenatal testing or preimplantation testing for subsequent pregnancies is necessary to identify possible pathogenic variants.

Prenatal diagnosis of ALPL gene mutations in recurrent fetal skeletal dysplasia.

OBJECTIVE: One multiparity women had recurrent pregnancies of skeletal dysplasia. The karyotype and array-comparative genomic hybridization were unremarkable. Thus, trio whole exome sequencings were suggested. CASE REPORT: The ALPL gene mutations were identified. Maternal heterozygous deletion on Chr1: 21880592 (GRCh37) TA->T, paternal heterozygous insertion on Chr1 21894597, 21894598 (GRCh37) G->GC, T->TAA, and the compound heterozygous mutation were noted on her third pregnancy. The prenatal ultrasound findings and ALPL variants were compatible with the diagnosis of hypophosphatasia. Sanger sequencings were performed and found their normal phenotype daughter carried the same heterozygous mutation with her mother. The mother was then incidentally found her fourth pregnancy; unfortunately, the fetus was prenatally diagnosed of hypophosphatasia with the compound heterozygous mutations. CONCLUSION: The whole exome sequencing could assist to find the disease-causing variants, which may not be identified through routine prenatal diagnosis. With the precise diagnosis, we could provide the counseling for prenatal or pre-implantation diagnosis.

Maternal-Neonatal Outcomes of Obstetric Deliveries Performed in Negative Pressure Isolation Rooms during the COVID-19 Omicron Variant Pandemic in Taiwan: A Retrospective Cohort Study of a Single Institution.

Objective: To investigate the maternal−neonatal outcomes of obstetric deliveries performed in negative pressure isolated delivery rooms (NPIDRs) during the coronavirus disease 2019 (COVID-19) omicron variant pandemic period in a single tertiary center in northern Taiwan. Methods: Confirmed positive and suspected-positive COVID-19 cases delivered in NPIDRs and COVID-19-negative mothers delivered in conventional delivery rooms (CDRs) in the period of 1 May 2022 to 31 May 2022 during the COVID-19 omicron variant pandemic stage were reviewed. The maternal−neonatal outcomes between the two groups of mothers were analyzed. All deliveries were performed following the obstetric and neonatologic protocols conforming to the epidemic prevention regulations promulgated by the Taiwan Centers for Disease Control (T-CDC). Multiple gestations, deliveries at gestational age below 34 weeks, and major fetal anomalies were excluded from this study. Results: A total of 213 obstetric deliveries were included. Forty-five deliveries were performed in NPIDRs due to a positive COVID-19 polymerase chain reaction (PCR) test (n = 41) or suspected COVID-19 positive status (n = 4). One hundred and sixty-eight deliveries with negative COVID-19 PCR tests were performed in CDRs. There was no statistical difference in maternal characteristics between the two groups of pregnant women. All COVID-19-confirmed cases either presented with mild upper-airway symptoms (78%) or were asymptomatic (22%); none of these cases developed severe acute respiratory syndrome. The total rate of cesarean section was not statistically different between obstetric deliveries in NPIDRs and in CDRs (38.1% vs. 40.0%, p = 0.82, respectively). Regardless of delivery modes, poorer short-term perinatal outcomes were observed in obstetric deliveries in NPIDRs: there were significant higher rates of neonatal respiratory distress (37.8% vs. 10.7%, p < 0.001, respectively), meconium-stained amniotic fluid (22.2% vs. 4.2%, p < 0.001, respectively) and newborn intensive care unit admission (55.6% vs. 8.3%, p < 0.001, respectively) in obstetric deliveries performed in NPIDRs than in CDRs. Maternal surgical outcomes were not significantly different between the two groups of patients. There was no vertical transmission or nosocomial infection observed in COVID-19 confirmed cases in this study period. Conclusions: Our study demonstrates that obstetric deliveries for positive and suspected COVID-19 omicron-variant cases performed in NPIDRs are associated with poorer short-term perinatal outcomes. Reasonable use of personal protective equipment in NPIDRs could effectively prevent nosocomial infection during obstetric deliveries for pregnant women infected with the COVID-19 omicron variant.

Effect of Fetoscopic Laser Photocoagulation on Fetal Growth and Placental Perfusion in Twin-Twin Transfusion Syndrome.

Objective: To investigate the fetal growth pattern after fetoscopic laser photocoagulation (FLP) in twin-twin transfusion syndrome (TTTS) and the effect of FLP on placental perfusion and intrauterine growth restriction (IUGR) incidence. Methods: TTTS cases with a live delivery of both twins at least 28 days after FLP and with a neonatal follow-up at our hospital at least 60 days after delivery were included. The biometric data obtained before FLP (based on ultrasound); time point M1), upon birth (M2), and at neonatal follow-up (M3) were analyzed. The body weight discordance (BWD) was defined as (estimated fetal weight [body weight] of the recipient twin − estimated fetal weight [body weight] of the donor twin)/(estimated fetal weight [body weight] of the recipient twin) × 100%. Total weight percentile (TWP) was defined as the donor + recipient twin weight percentile; the TWP indirectly reflected the total placental perfusion. Results: the BWDs decreased from M1 to M2 to M3 (24.6, 15.9, and 5.1, respectively, p < 0.001, repeated measurements). The weight percentiles of recipient twins decreased after FLP, that is, from M1 to M2 (53.4% vs. 33.6%, respectively, p < 0.001, least significant difference [LSD] test). However, the weight percentiles of donor twins increased after delivery, that is, from M2 to M3 (13.2% vs. 26.2%, respectively, p < 0.001, LSD test). Moreover, the TWPs decreased after FLP, that is, from M1 to M2 (66.2% vs. 46.8%, respectively, p = 0.002, LSD test) and increased after delivery, that is, from M2 to M3 (46.8% vs. 63.2%, respectively, p = 0.024, LSD test). The IUGR incidences in donor twins were significantly lower after FLP (77.4% vs. 56.6%, respectively, p = 0.019, McNemar test) and further decreased after delivery (56.6% vs. 37.7%, respectively, p = 0.041, McNemar Test); however, no significant difference was observed in recipient twins' IUGR incidences among M1, M2, and M3. The donor twin had catch- up growth in body weight, height, and head circumference after delivery, and the recipient twin had catch-up growth in only body height after delivery. Conclusions: the BWD decreased after FLP in fetuses with TTTS mainly because of the decreased weight percentiles of recipient twins. Moreover, it further decreased after delivery mainly because of the increased weight percentiles of donor twins. FLP not only decreased placental perfusion but also improved the TTTS prognosis because of reduced BWD and donor twin IUGR incidence.

Effect of Hypoxia on Glucose Transporter 1 and 3 Gene Expression in Placental Mesenchymal Stem Cells Derived from Growth-Restricted Fetuses.

(1) Background: Glucose is transferred from maternal blood to the fetus by glucose transporters. What is the effect of hypoxia on the gene expression of placenta glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in growth-restricted fetus is interesting. (2) Methods: The gene expression of GLUT1 and GLUT3 and the protein expression of HIF-1α were evaluated under nonhypoxic conditions and after 4 and 8 h under hypoxic conditions in placental mesenchymal stem cells derived from monochorionic twin pregnancies with selective intrauterine growth restriction. (3) Results: The gene expressions of GLUT1 and GLUT3 under hypoxia conditions were higher in placental mesenchymal stem cells derived from appropriate-for-gestational-age fetuses than in those from selective intrauterine growth-restricted fetuses. However, the protein expression of hypoxia induced factor-1 α (HIF-1α) at hypoxia condition was not lower in placenta mesenchymal stem cells from selective intrauterine growth-restricted fetuses than in placental mesenchymal stem cells from appropriate-for-gestational-age fetuses. (4) Conclusions: Hypoxia-induced upregulation of GLUT1 and GLUT3 expression was decreased in placental mesenchymal stem cells from selective intrauterine growth-restricted fetuses but not due to decreased HIF-1α expression. Selective growth-restricted fetuses have less capacity for hypoxia-induced upregulation of placental glucose transport.

Association between respiratory distress syndrome of newborns and fetal growth restriction evaluated using a dichorionic twin pregnancy model.

AIMS: To evaluate the association between respiratory distress syndrome (RDS) and intrauterine fetal growth restriction (IUGR) by using a dichorionic twin model. METHODS: We retrospectively analyzed twins delivered between September 2012 and December 2018. A dichorionic (DC) twin pregnancy with selective IUGR (sIUGR) was defined as the presence of (i) a birthweight discordance of ≥25% and (ii) a smaller twin with birth weight below the 10th percentile. Pregnancies with major fetal anomalies, delivery at gestational age below 23 weeks, and intrauterine fetal demise were excluded. RESULTS: We included 53 DC twins with sIUGR. The sIUGR twin had a higher risk of RDS than did his appropriate for gestational age (AGA) cotwin (32.1% vs. 11.3%, p = 0.001); however, the risk of severe RDS did not significantly differ between the twins (17.0% vs 9.4%, p = 0.125). The findings of logistic regression analysis indicated that younger gestational age (weeks) at delivery (odds ratio = 0.48, p < 0.001) and IUGR (odds ratio = 13.87, p = 0.009) were significant risk factors for RDS in newborns in DC twin pregnancies with selective sIUGR. CONCLUSIONS: IUGR was identified as a risk factor for newborn RDS. However, the association between IUGR and severe newborn RDS was not significant possibly due to the small sample size of this study.

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).

Prenatal Diagnosis of Placental Mesenchymal Dysplasia with 46, X, Isochromosome Xq/45, X Mosaicism.

Placental mesenchymal dysplasia is an uncommon vascular anomaly of the placenta with characteristics of placentomegaly and multicystic appearance and with or without association with fetal chromosomal anomaly. We present a unique placental mesenchymal dysplasia patient with amniotic fluid karyotyping as 46, X, iso(X) (q10). Detailed molecular testing of the amniotic fluid, fetal cord blood, non-dysplastic placenta and dysplastic placenta was conducted after termination of pregnancy, from which we proved biparental/androgenetic (46, X, i(X) (q10)/45, X) mosaicism in different gestational tissues. A high portion of androgenetic cells in dysplastic placenta (74.2%) and near 100% of biparental cells in the fetus's blood and amniotic fluid were revealed. Delicate mosaic analyses were performed, and possible pathogenesis and embryogenesis of this case were drawn up.

Frequency and clinical significance of chromosomal inversions prenatally diagnosed by second trimester amniocentesis.

To compare the frequency and clinical significance of familial and de novo chromosomal inversions during prenatal diagnosis. This was a retrospective study of inversions diagnosed prenatally in an Asian population by applying conventional GTG-banding to amniocyte cultures. Data from 2005 to 2019 were extracted from a single-center laboratory database. The types, frequencies, and inheritance patterns of multiple inversions were analyzed. Pericentric variant inversions of chromosome 9 or Y were excluded. In total, 56 (0.27%) fetuses with inversions were identified in the 15-year database of 21,120 confirmative diagnostic procedures. Pericentric and paracentric inversions accounted for 62.5% (35/56) and 37.5% of the inversions, respectively. Familial inversions accounted for nearly 90% of cases, and de novo mutation was identified in two pericentric and two paracentric cases. Inversions were most frequently identified on chromosomes 1 and 2 (16.1% of all inversions), followed by chromosomes 6, 7, and 10 (8.9% of all cases). The indications for invasive testing were as follows: advanced maternal age (67.3%), abnormal ultrasound findings (2.1%), abnormal serum aneuploidy screening (20.4%), and other indications (10.2%). The mode of inheritance was available for 67.9% of cases (38/56), with 89.5% of inversions being inherited (34/38). A slight preponderance of inheritance in female fetuses was observed. Three patients with inherited inversions opted for termination (two had severe central nervous system lesions and one had thalassemia major). Gestation continued for 53 fetuses, who exhibited no structural defects at birth or significant developmental problems a year after birth. Our study indicates that approximately 90% of prenatally diagnosed inversions involve familial inheritance, are spreading, and behave like founder effect mutations in this isolated population on an island. This finding can help to alleviate anxiety during prenatal counseling, which further underscores the importance of parental chromosomal analysis, further genetic studies, and appropriate counseling in cases where a nonfamilial inversion is diagnosed.

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.

Hydrometrocolpos in Infants: Etiologies and Clinical Presentations.

Hydrometrocolpos (HMC) is a rare condition where fluids or secretions accumulate in the vagina (hydrocolpos) or up to the uterus (hydrometrocolpos). This case series study reports three infants with different etiologies and presentations of HMC and aims to review literature for proper workup upon initial diagnosis. The first neonate antenatally presented with a huge cystic mass. HMC secondary to imperforate hymen was proved, and hymenotomy was performed at 2 days of age. The second participant presented with persistent urogenital sinus and hematopoietic chimerism, possibly due to transfusion from her twin brother via placenta anastomoses. At 2 months of corrected age, she had difficult defecating, and sonogram revealed HMC with normal appearance of uterus and ovaries. Regular follow-ups and surgical reconstruction will be conducted before puberty. The third patient had cloacal malformation and multiple congenital anomalies at birth. Vesicovaginal fistula-related HMC was detected and managed with surgical drainage in the neonate stage. The girl began menstruation with dysmenorrhea at 12 years. The image studies demonstrated hematometrocolpos secondary to left-side hemivaginal septum, uterine didelphy, and ipsilateral renal agenesis, indicating Herlyn-Werner-Wunderlich syndrome. HMC can be diagnosed easily via sonogram. Careful external genitalia examinations help to identify persistent urogenital sinus or cloacal malformation. Occasionally, the HMC may be part of syndrome manifestations or associated with sex chromosome anomalies. Clinicians may conduct surveillance of renal, cardiac, and skeletal systems as well as chromosome study for early diagnosis and management.

Effectiveness of a Nurse-Led Web-Based Health Management in Preventing Women With Gestational Diabetes From Developing Metabolic Syndrome.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are more likely to develop metabolic syndrome (MS). However, the effectiveness of web-based health management in preventing women at high risk of GDM from developing MS has rarely been studied. PURPOSE: The aim of this study was to evaluate the longitudinal effects of nurse-led web-based health management on maternal anthropometric, metabolic measures, and neonatal outcomes. METHODS: A randomized controlled trial was conducted from February 2017 to February 2018, in accordance with the Consolidated Standards of Reporting Trials guidelines. Data were collected from 112 pregnant women at high risk of GDM who had been screened from 984 potential participants in northern Taiwan. Participants were randomly assigned to the intervention group (n = 56) or the control group (n = 56). The intervention group received a 6-month nurse-led, web-based health management program as well as consultations conducted via the LINE mobile app. Anthropometric and metabolic measures were assessed at baseline (Time 0, prior to 28 weeks of gestation), Time 1 (36-40 weeks of gestation), and Time 2 (6-12 weeks of postpartum). Maternal and neonatal outcomes were assessed at delivery. Clinical trial was registered. RESULTS: Analysis using the general estimating equation models found that anthropometric and metabolic measures were significantly better in the intervention group than the control group and varied with time. At Time 1, the levels of diastolic pressure (ß = -4.981, p = .025) and triglyceride (TG; ß = -33.69, p = .020) were significantly lower in the intervention group than the control group, and at Time 2, the incidence of MS in the intervention group was lower than that in the control group (χ2 = 6.022, p = .014). The number of newborns with low birth weight in the intervention group was lower than that in the control group (χ2 = 6.729, p = .012). CONCLUSION/IMPLICATIONS FOR PRACTICE: This nurse-led, web-based health management was shown to be effective in improving MS outcomes and may play an important role and show feasible clinical value in changing the current pregnancy care model.

Laser therapy for twin-twin transfusion syndrome in a dizygotic monochorionic twin pregnancy: A case report.

OBJECTIVE: A monochorionic dizygotic (MCDZ) twin is rare, especially when complicated with twin-twin transfusion syndrome (TTTS) and treated by laser therapy. CASE REPORT: A pregnancy achieved from oocyte donation and intracytoplasmic sperm injection resulted in two embryos transferred. A monochorionic diamniotic twin pregnancy was diagnosed by an early ultrasound; however, at 16 weeks of gestation, instead of the same sex, the ultrasound suspected there was sex discrepancy between the twins. TTTS with severe polyhydramnios occurred at 22 weeks, leading to a laser therapy, which was followed with a smooth post-operation course. Then the Cesarean section was performed at the gestational age of 29 weeks due to severe preeclampsia, giving birth to two live newborns: one female and one male baby both without neurological sequelae at the time of discharge. Blood chromosomes obtained at delivery and 65 days after delivery all revealed an XX and XY chimera from both babies. CONCLUSION: Laser therapy is also effective in MCDZ twin complicated with TTTS. Determination of chorionicity in early pregnancy could timely prompt us to watch out for complications unique to monochorionic twin pregnancy.

Delivery management of suspected or confirmed COVID-19 positive mothers.

The Coronavirus Disease-2019 (COVID-19) pandemic has brought catastrophic impact on the world since the beginning of December 2019. Extra precautionary measures against COVID-19 during and after delivery are pivotal to ensure the safety of the baby and health care workers. Based on current literature, it is recommended that delivery decisions be discussed between obstetricians and neonatologists prior to delivery, and designated negative pressure delivery rooms should be arranged for COVID person under investigation (PUI). During delivery, a minimal number of experienced staff attending delivery should don personal protective equipment (PPE) and follow the neonatal resuscitation program (NRP). Positive pressure ventilation is best used in a negative pressure room if available. At-risk babies should be transported in an isolette, and tested for COVID-19 in a negative pressure room soon after bathing. Skin-to-skin contact and breast milk feed should continue under certain circumstances. Although newborns with COVID-19 infections often present with symptoms that mimic sepsis and one third of affected patients may demand some form of respiratory support, short-term prognoses are favorable and most recover within two weeks of symptoms onset. In this article, we will further elaborate on topics covering timing and mode of delivery, antenatal steroid, vertical transmission, delivery room management, airway management, transport, testing and isolation after birth, skin-to-skin contact, breast milk feeding, clinical features, outcomes, and discharge plans. In addition, we also share our experiences of encountering neonates born of suspected COVID-19 positive mothers.

Association between intrauterine growth restriction and patent ductus arteriosus: Use of a dichorionic twin pregnancy model.

OBJECTIVE: To evaluate the association between intrauterine growth restriction (IUGR) and the incidence of fetuses with patent ductus arteriosus (PDA) and Hemodynamically significant PDA (Hs-PDA) in dichorionic twins (DC) with selective IUGR. MATERIALS AND METHODS: This is an observational cohort study and retrospective case assessment, involved twins born at Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan between 2013 and 2018. DC twins with selective IUGR (sIUGR) were defined as the presence of a birth weight discordance of >25% and a smaller twin with a birth weight below the tenth percentile. PDA was diagnosed using echocardiography between postnatal day 3 and 7. Hs-PDA was defined as PDA plus increased pulmonary circulation, poor systemic perfusion, cardiomegaly, pulmonary edema, or hypotension requiring pharmacotherapeutic intervention. RESULT: A total of 1187 twins were delivered during the study period, and 53 DC twins with selective IUGR were included in this study. DC twins with PDA have higher rate of preterm birth, lower gestational age of delivery, and lower mean birth weight of both twins compared with DC twins without PDA. In a comparison of the sIUGR twin with the appropriate for gestational age co-twin, both the incidences of PDA (28.30% vs. 7.55%, respectively; P = 0.003) and Hs-PDA (24.53% vs. 5.66%, respectively; P = 0.002) were higher in sIUGR fetuses than in the appropriate for gestational age co-twins. Small gestational age of delivery was the only variable to predict PDA and Hs-PDA [p = 0.002, Odds ratio = 0.57 (0.39-0.82), p = 0.009, Odds ratio = 0.71 (0.55-0.92), respectively]. CONCLUSION: An analysis of dichorionic twins with sIUGR indicated that IUGR increased the risk of PDA and hemodynamically significant PDA.

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.