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Objective: Kleefstra Syndrome (KS) is a rare genetic disorder caused by a deletion at 9q34.3. Studies showed that various heart defects are observed in 41–43% of patients and abnormal features on brain imaging in 58–63%. To date, the prenatal phenotype in KS has yet to be defined. Case report: We present the first prenatal diagnosis and chromosomal microarray analysis (CMA) of a case of 9q34.3 microdeletion in a fetus with increased amniotic fluid, supported by abnormal prenatal ultrasound findings, and confirmed via autopsy. CMA revealed a 2.1 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1, which is consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome. Conclusion: When a fetus with normal karyotype presents with polyhydramnios or abnormalities noted during second-trimester prenatal ultrasound screening, CMA analysis can be considered as the next step to rule out or confirm the diagnosis of chromosomal or other genetic aberrations.

Background: Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity. Methods: We enrolled 222 parturient (gestational age 34–42 weeks) women aged 20–46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68. Results: The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p

Background: The rate of induction of labour has increased over the decades and numerous medications are available in the market. This study compares the efficacy and safety between dinoprostone slow-release pessary (Propess) and dinoprostone tablet (Prostin) for labour induction at term in nulliparous women. Methods: This was a prospective single-blind randomized controlled trial conducted in a tertiary medical centre in Taiwan from September 1, 2020 to February 28, 2021. We recruited nulliparous women at term with a singleton pregnancy, fetus in cephalic presentation, an unfavourable cervix, and the cervical length had been measured by transvaginal sonography three times during labour induction. The main outcomes are duration from induction of labour to vaginal delivery, vaginal delivery rate, maternal and neonatal complication rates. Results: In both groups, Prostin and Propess, 30 pregnant women were enrolled. The Propess group had higher vaginal delivery rate but it did not meet statistically significant difference. The Prostin group had significantly higher rate of adding oxytocin for augmentation (p = 0.0002). No significant difference was observed in either labouring course, maternal or neonatal outcomes. The probability of vaginal delivery was independently related to the cervical length measured by transvaginal sonography 8 h after Prostin or Propess administration as well as neonatal birth weight. Conclusion: Both Prostin and Propess can be used as cervical ripening agents with similar efficacy and without significant morbidity. Propess administration was associated with higher vaginal delivery rate and less need to add oxytocin. Intrapartum measurement of cervical length is helpful in predicting successful vaginal delivery.

Objective: Moyamoya disease (MMD) is a rare cerebral vascular disease and there is limited clinical experience for pregnant women. Cerebrovascular condition might deteriorated during pregnancy. Management and mode of delivery is challenging for obstetrics specialist. Case report: Three cases of parturients with moyamoya disease delivered in National Taiwan University Hospital are presented. All were previously diagnosed and one had stroke incidence before current pregnancy course. Two delivered with Cesarean section and one with vaginal delivery, and all delivered at term without maternal or neonatal complication. Conclusion: Although delivery method of parturients with MMD has been debating, vaginal delivery may be suitable for certain cases under adequate monitoring and case selection.

Abstract Hoyeraal-Hreidarsson syndrome (HHS) is the most severe form of dyskeratosis congenita (DC) and is caused by mutations in genes involved in telomere maintenance. Here, we identified male siblings from a family with HHS carrying a hemizygous mutation (c.1345C > G, p.R449G), located in the C-terminal nuclear localization signal (NLS) of the DKC1 gene. These patients exhibit progressive cerebellar hypoplasia, recurrent infections, pancytopenia due to bone marrow failure, and short leukocyte telomere lengths. Single-cell RNA sequencing analysis suggested defects in the NLRP3 inflammasome in monocytes and the activation and maturation of NK cells and B cells. In experiments using induced pluripotent stem cells (iPSCs) from patients, DKC1_R449G iPSCs had short telomere lengths due to reduced levels of human telomerase RNA (hTR) and increased cytosolic proportions of DKC1. Treatment with dihydroquinolizinone RG7834 and 3′deoxyanosine cordycepin rescued telomere length in patient-derived iPSCs. Together, our findings not only provide new insights into immunodeficiency in DC patients but also provide treatment options for telomerase insufficiency disorders.

Background: Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. Methods: This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. Results: 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). Conclusion: The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.

Abstract Background The short arm of chromosome 16 consists of several copy number variants (CNVs) that are crucial in neurodevelopmental disorders; however, incomplete penetrance and diverse phenotypes after birth aggravate the difficulty of prenatal genetic counseling. Methods We screened 15,051 pregnant women who underwent prenatal chromosomal microarray analysis between July 2012 and December 2017. Patients with positive array results were divided into four subgroups based on the type of mutation identified on screening (16p13.3, 16p13.11, 16p12.2, and 16p11.2), and the maternal characteristics, prenatal examinations, and postnatal outcomes of different cases were reviewed. Results Chromosome 16 CNVs were identified in 34 fetuses, including four with 16p13.3 CNVs, 22 with 16p13.11 CNVs, two with 16p12.2 microdeletions, and six with 16p11.2 CNVs. Of the 34 fetuses, 17 delivered without early childhood neurodevelopmental disorders, three developed neurodevelopmental disorders during childhood, and 10 were terminated. Conclusion Incomplete penetrance and variable expressivity make prenatal counseling challenging. Most cases with inherited 16p13.11 microduplication were reported to have normal development in early childhood, and we also report a few cases of de novo 16p CNVs without further neurodevelopmental disorders.

Objective: The transcription activator FOXM1 was found to be essential for beta cell expansion and glucose homeostasis during pregnancy in a mouse model. We assumed that the mechanism would be similar in humans. Thus, we aimed to determine the correlation, if any, between FOXM1 and gestational diabetes mellitus in pregnant women. Materials and methods: Participants were recruited and collected from a single tertiary medical center in Taiwan. Participants' maternal peripheral blood was retrieved upon their admission for labor. The postpartum cord blood was harvested within 5 min after delivery of the fetus to test the FOXM1 mRNA expression level, as well as glucose, insulin, and C-peptide protein concentrations. Result: We recruited 83 pregnant women, 63 without GDM and 20 with GDM. The non-GDM maternal samples had a FOXM1ΔCt of 9.2 ± 1.53, whereas it was 8.92 ± 1.48 in the GDM group (p = 0.504). In the cord blood group, the GDM and non-GDM FOXM1ΔCt were 7.7 ± 1.02 and 7.95 ± 1.56, respectively (p = 0.416). Conclusion: This is the first study to prove a relationship between FOXM1 and GDM in humans. Although the exact linear correlation is still unknown, our results may provide an impetus for further research.

BackgroundHyperglycemia in pregnancy (HIP) increases the risk of adverse pregnancy outcomes. The increasing prevalence of overweight or obesity and the increasing proportion of pregnant women with advanced maternal age (AMA) in the recent decade may affect its prevalence. We analyzed the secular trend of HIP prevalence in 2008-2017 in Taiwan and investigated the impact of AMA in this study.MethodsThis cross-sectional study used data from Health and Welfare Data Science Center. Pregnant women who registered their data in the Birth Certificate Application in 2008-2017 were recruited. Diagnosis of HIP was defined by ICD-9-CM and ICD-10-CM codes.ResultsIn 2008-2017, 151,306-211,768 pregnant women were recruited in different years. The proportion of women with AMA increased from 15.8% to 32.1%. Meanwhile, the prevalence increased from 0.5% to 0.9% for preexisting diabetes, 0.2% to 0.4% for undiagnosed diabetes, and 11.4% to 14.5% for GDM. Maternal age was significantly associated with the prevalence of HIP. For women aged

Purpose: To evaluate the effectiveness of adding carbetocin to regular uterotonic agents for prevention of postpartum hemorrhage (PPH) after cesarean section for twin pregnancies. Methods: This is a retrospective uncontrolled before-after study done in a tertiary center in Taiwan, 2010–2017. Women with twin pregnancies that underwent cesarean section were enrolled. The control group (n = 114) received oxytocin infusion and direct uterine injection. In addition to these, the study group (n = 127) received 100ug of intravenous carbetocin. Primary endpoint was the change in hemoglobin. Secondary endpoints included risk of PPH and undiagnosed PPH (Hb dropped more than 2 g/dL), blood loss, the need for additional uterotonic maneuvers, and blood transfusion. Hemodynamic changes were also investigated. Results: After adjusting for confounding factors, the change in Hb (0.35 g/dL, 95% CI: −0.03∼0.74) and incidence of PPH (OR 0.30, 95% CI: 0.03∼3.28) were comparable in both groups. However, women with undiagnosed PPH decreased (OR 0.43, 95% CI:0.22∼0.85). Total blood loss in 24 h after delivery also decreased (−40.33 mL, 95%CI: −80.32∼ −0.34). The use of extra uterotonic medications and the need for blood transfusion did not differ. The systolic blood pressure 4 h after childbirth was higher in the carbetocin group (6.71, 95% CI: 2.27∼11.15). Conclusion: The use of carbetocin in addition to regular uterotonic agents decreased total blood loss and undiagnosed PPH. Also, systolic blood pressure 4 h after childbirth is higher in the carbetocin group. There was no significant difference in hemoglobin change and risk of PPH.

BackgroundGestational adaptation occurs soon after fertilization and continues throughout pregnancy, whereas women return to a pre-pregnancy state after delivery and lactation. However, little is known about the role of DNA methylation in fine-tuning maternal physiology. Understanding the changes in DNA methylation during pregnancy is the first step in clarifying the association of diet, nutrition, and thromboembolism with the changes in DNA methylation. In this study, we investigated whether and how the DNA methylation pattern changes in the three trimesters and after delivery in ten uncomplicated pregnancies.ResultsDNA methylation was measured using a Human MethylationEPIC BeadChip. There were 14,018 cytosine-guanine dinucleotide (CpG) sites with statistically significant changes in DNA methylation over the four time periods (p < 0.001). Overall, DNA methylation after delivery was higher than that of the three trimesters (p < 0.001), with the protein ubiquitination pathway being the top canonical pathway involved. We classified the CpG sites into nine groups according to the changes in the three trimesters and found that 38.37% of CpG sites had DNA methylation changes during pregnancy, especially between the first and second trimesters.ConclusionDNA methylation pattern changes between trimesters, indicating possible involvement in maternal adaptation to pregnancy. Meanwhile, DNA methylation patterns during pregnancy and in the postpartum period were different, implying that puerperium repair may also function through DNA methylation mechanisms.

Objective: We present prenatal diagnosis low-level mosaic trisomy 17 with maternal uniparental disomy (UPD) 17 at amniocentesis in a pregnancy with a favorable outcome. Materials and methods: A 40-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 47,XX,+17 [13]/ 46, XX [23]. Repeat amniocentesis was performed at 21 weeks of gestation. Conventional cytogenetic analysis was applied on cultured amniocytes, parental bloods and cord blood. Simultaneous molecular genetic analysis such as interphase fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) assays were applied on uncultured amniocytes. Interphase FISH was applied on postnatal buccal cells. Results: Repeat amniocentesis revealed a karyotype of 47,XX,+17[6]/46,XX[28]. Genetic analyses on uncultured amniocytes showed the results of mosaic trisomy 17 (12/101 cells = 11.9%) in FISH analysis, no genomic imbalance in aCGH analysis and maternal UPD 17 in QF-PCR assays. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a 1449-g, phenotypically normal female baby was delivered prematurely at 31 weeks of gestation. The cord blood had a karyotype of 46,XX. She had a normal psychomotor development at age 22 months at follow-up. Interphase FISH analysis on buccal cells showed trisomy 17 signals in 1/66 cells (1.5%). Conclusions: Low-level mosaicism for trisomy 17 associated with maternal UPD 17 detected by amniocentesis without ultrasound abnormality can be associated with a favorable outcome. Molecular genetic analysis of uncultured amniocytes at repeat amniocentesis is useful for confirmation and genetic counseling under such as circumstance. Keywords: amniocentesis, Maternal uniparental disomy 17, Mosaic trisomy 17, Prenatal diagnosis

Prenatal genetic counseling of fetuses diagnosed with 15q11.2 copy number variants (CNVs) involving the BP1–BP2 region is difficult due to limited information and controversial opinion on prognosis. In total, we collected the data of 36 pregnant women who underwent prenatal microarray analysis from 2010 to 2017 and were assessed at National Taiwan University Hospital. Comparison of the maternal characteristics, prenatal ultrasound findings, and postnatal outcomes among the different cases involving the 15q11.2 BP1–BP2 region were presented. Out of the 36 fetuses diagnosed with CNVs involving the BP1–BP2 region, five were diagnosed with microduplications and 31 with microdeletions. Among the participants, 10 pregnant women received termination of pregnancy and 26 gave birth to healthy individuals (27 babies in total). The prognoses of 15q11.2 CNVs were controversial and recent studies have revealed its low pathogenicity. In our study, the prenatal abnormal ultrasound findings were recorded in 12 participants and were associated with 15q11.2 deletions. No obvious developmental delay or neurological disorders were detected in early childhood.

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

Background: Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) has become an essential global health issue and its elimination is a crucial target. A prenatal “opt-out” HIV screening program was initiated in 2005 in Taiwan. In recent 3 years, approximate screening and MTCT rates were 99% and 2.27% (1/44), respectively. Here, we describe the clinical management of mothers infected with HIV and MTCT rate at National Taiwan University Hospital (NTUH), Taipei, Taiwan, in the years after the program was initiated. Methods: We retrospectively reviewed charts of pregnant women infected with HIV, who were managed at NTUH between January 2005 and December 2016. HIV infection status of 39 infants born to mothers infected with HIV was available. Results: Between 2005 and December 2016, 50 pregnant women infected with HIV, with 57 parities were managed at NTUH, and 57 live infants were born. We excluded 18 parities because of missing data. Maternal antiviral treatment was administered in 37 of 39 infants. Only one infant tested positive for an HIV antibody test at 18 months, but showed definitive HIV exclusion at 20 months after a series of tests without administration of antiviral treatment. MTCT rate was 0%. Conclusion: Successful implementation of available perinatal HIV intervention dramatically reduced vertical transmission rate of HIV. MTCT rate was 0% in NTUH after the program. However, as NTUH is an HIV referral center, additional efforts are needed to achieve the World Health Organization criteria of lowering the vertical transmission rate of HIV to

Purpose: To assess the complication rates following chorionic villus sampling (CVS) and midtrimester amniocentesis in Taiwan. Methods: This is a national registry-based cohort study from Taiwan. We included all women with singleton pregnancies who received either CVS (n = 1409) or midtrimester amniocentesis (n = 250,566) during 2006–2012. We assessed preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD), infection and spontaneous abortion (SA) that occurred within fourteen days after the procedures. We also assessed the risks of preterm delivery and miscarriage before 24 gestational weeks after amniocentesis. These complications were collected from the Genetic Disease Database of the Ministry of Health and Welfare, Taiwan National Birth Certificate Registry, and the Taiwan National Health Insurance Database. Pearson χ2 tests were used to compare the distributions between groups. Results: For patients who underwent midtrimester amniocentesis, the rates of PPROM, IUFD, infection and SA within fourteen days were 0.24%, 0.11%, 0.05%, and 0.05%, respectively. Women with a normal fetal karyotype had a preterm birth rate (

Paternal uniparental disomy 14 (UDP(14)pat) is a rare imprinting disorder with a set of unique neonatal clinical features documented, including craniofacial abnormalities, thoracic and abdominal wall defects, and polyhydraminos. To date, no studies focus on prenatal diagnosis of uniparental disomy have been published. We report a case of a fetus with abnormal ultrasound features at 18 weeks of gestation and normal karyotype result. Subsequent Single nucleotide polymorphism (SNP)-based Affymetrix 750K Microarray analysis revealed the complete loss of heterozygosity for chromosome 14, identifying a case of uniparental disomy. Postmortem examination of the aborted fetus at 21 weeks, coupled with further Affymetrix 750K microarray analysis on the parents, confirmed the diagnosis of parental uniparental disomy for chromosome 14. Keywords: Paternal uniparental disomy 14, Prenatal diagnosis, Uniparental disomy

AimThe addition of maternal age to fasting plasma glucose (FPG) at 24-28 gestational weeks improves the performance of GDM screening as maternal age increases. However, this method delays the diagnosis of GDM. Since FPG at the first prenatal visit (FPV) is a screening option for pre-existing diabetes, we evaluated the performance of age plus FPG at the FPV to reduce the need for the OGTT.MethodsPregnant women were recruited consecutively in 2013-2018 (the training cohort) and 2019 (the validation cohort). We excluded women with twin pregnancies, unavailable FPG at the FPV or OGTT data, pre-pregnancy diabetes, or a history of GDM. All participants underwent FPG and haemoglobin A1c (HbA1c) at the FPV and received 75-g OGTT at 24-28 gestational weeks if FPG at the FPV was ResultsThe incidence of GDM increased with age. The "FPG at the FPV" algorithm reduced OGTT% to 68.8% with the FPG cutoff at 79 mg/dl. The "age plus FPG at the FPV" algorithm, with the cutoff of 114, further reduced OGTT% to 58.3%, with the sensitivity of 90.7% (9.3% GDM missed) and the specificity of 100%. These findings were replicated in the validation cohort.ConclusionsScreening GDM by maternal age plus FPG at the FPV can reduce OGTT%, especially in populations with a significant proportion of pregnant women with advanced ages.

We present a rare male fetus with karyotype of mosaic 45,X that comprises two types of aberrant Y chromosomes arising de novo (Yq12 deletion and isodicentric Yq11.22). Both types of the aberrant Y chromosomes lack the AZFc region which are expected to result in oligospermia but unaffected male external genitalia. Genetic analyses by karyotyping, chromosome microarray (CMA), and multiplex ligation-dependent probe amplification (MLPA) for the fetus revealed conflicting results. Additional molecular cytogenetics tools including fluorescence in situ hybridization (FISH) and multicolor banding (mBAND) were performed, which help resolving the discrepancy and delineated the composition of the aberrant Y chromosomes. This report highlighted the importance of incorporating multiple genetic technologies for accurate characterization of complex chromosomal rearrangements, which aid in the prenatal diagnosis and genetic counseling. Keywords: AZF, CMA, FISH, idic(Y), Karyotyping, mBAND

Sensorineural hearing impairment is a common sensory deficit in children and more than 50% of these cases are caused by genetic etiologies, that is, hereditary hearing impairment (HHI). Recent advances in genomic medicine have revolutionized the diagnostics of, and counseling for, HHI, including preimplantation genetic diagnosis (PGD), thus providing parents-to-be with better reproductive choices. Over the past decade, we have performed PGD using the amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) technique in 11 couples with a history of HHI, namely eight with GJB2 variants, one with OTOF variants, one with SLC26A4 variants, and one with an MITF variant. We demonstrated that PGD can be successfully applied to HHI of different inheritance modes, namely autosomal dominant or recessive, and phenotypes, namely syndromic or non-syndromic HHI. However, certain ethical concerns warrant scrutiny before PGD can be widely applied to at-risk couples with a history of HHI.

Objective: Termination of pregnancy in midtrimester can be performed surgically or medically. The aim of this study was to evaluate the medical methods, and the additional efficacy of using a transcervical double-balloon catheter in midtrimester termination. Materials and methods: In this retrospective study, we included 167 pregnant women admitted during the period from January 1, 2011, to June 31, 2015, who were between 14 weeks and 28 weeks of gestation, and underwent intended termination of pregnancy at our center. Each of the 167 patients was allocated to either the cervical ripening balloon (CRB) group (with double-balloon catheter) or the non-CRB (without double-balloon catheter) group, by the choice or preference of the patient and her attending physician. Termination of pregnancy in the CRB group (72 patients) was conducted by placing a transcervical double-balloon catheter (COOK CRB), with both the uterine and vaginal balloons inflated with 30–80 mL of normal saline, and held in place for 12 hours, whereas in the non-CRB group (95 patients) vaginal and oral misoprostol alone were administered. Results: There were no significant differences between the CRB and non-CRB groups with regard to induction-to-delivery time (23.1 hours vs. 21.1 hours) and successful abortion rate within 30 hours (80.0% vs. 83.7%). There were no severe complications in both groups. Conclusion: There was no significant additional benefit of using a double-balloon catheter in midtrimester termination of pregnancy, although the technique was considered simple and generally well-tolerated. Placing a transcervical double-balloon catheter could be the primary method, or one of the alternative medical methods if the patient and/or obstetrician prefers no operation.

Objective: The association of interleukin-10 (IL-10) polymorphism with diabetes and its complication was recently established, while there were few researches considering the potential role of IL-10 in gestational diabetes (GDM). This study aimed to investigate the association between IL-10 gene rs1800896 (−1082 A/G), rs1800871 (−819 T/C), rs1800872 (−592 A/C), and rs3021094 (3388 A/C) single nucleotide polymorphisms (SNPs) and GDM susceptibility.Methods: This study included 72 GDM patients and 100 healthy pregnant women. Direct sequencing of the products from polymerase chain reactions of the extracted genomic DNA from study subjects were conducted for analyzing IL-10 gene polymorphism and further genotype frequencies were compared. Plasma IL-10 concentration was measured by ELISA method.Results: The results revealed no significant difference in −592 A/C, −819 T/C, and −1082 A/G genotypes. Significantly increased prevalence of A allele (P = 0.028, OR = 1.69, 95% CI = 1.081–2.64) and A/A genotype (P = 0.031, OR = 2.881, 95% CI = 1.145–7.250) at a previously un-characterized rs3021094 SNP were discovered in the GDM group. Increased IL-10 levels and insulin resistance were also related to the genotype of rs3021094. The risk of GDM was increased when IL-10 level was over 6.5 pg/ml.Conclusion: Our study demonstrated that A allele and A/A genotype of rs3021094 SNP in IL-10 gene were linked to increased risk for GDM, IL-10 plasma level and insulin resistance, which could be potential targets for early screening and detection of GDM.

AimOverweight and obesity are important risk factors of gestational diabetes mellitus (GDM). Clustering of metabolic risk factors in early pregnancy may be a potential pathogenesis between the link of overweight/obesity and GDM. Since it remains unexplored, we investigated if overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM in this cohort study.MethodsTotal 527 women who visited National Taiwan University Hospital for prenatal care in between November 2013 to April 2018 were enrolled. Risk factors of GDM in the first prenatal visit (FPV) were recorded. Overweight/obesity was defined if body mass index ≥24 kg/m2. GDM was diagnosed from the result of a 75g oral glucose tolerance test in 24-28 gestational weeks.ResultsOverweight/obesity was associated with clustering of metabolic risk factors of GDM, including high fasting plasma glucose, high HbA1c, insulin resistance, high plasma triglyceride and elevated blood pressure in FPV (pConclusionsOverweight/obesity is associated with clustering of metabolic risk factors in early pregnancy, which is correlated with higher risk of GDM. Our findings suggest that metabolic risk factors during early pregnancy should be evaluated in overweight/obese women.

Objective: This study investigated the pregnancy outcomes of women who had undergone kidney transplantations from 1992 to 2013 in a single medical center. Materials and Methods: Records for patients who had undergone kidney transplantations between 1992 and 2013 at National Taiwan University Hospital, Taipei, Taiwan were retrospectively reviewed, and data on obstetric conditions, neonatal outcomes, and maternal and neonatal complications were collected. Results: Data for a total of 15 pregnancies in 13 women who had undergone kidney transplantation between 1992 and 2013 were included in this study. The live birth rate was 87%. The mean gestational age was 35.4 ± 3.2 weeks, and the mean birth body weight was 2208.8 ± 678.8 g. Forty percent of the neonates were small for their gestational age (< 10th percentile); 53.3% of the pregnancies resulted in preterm deliveries (< 37 weeks); and 26.7% of the neonates needed Neonatal Intensive Care Unit admission. The prevalence rates of preeclampsia and gestational diabetes were 23.0% and 13.3%, respectively. Conclusion: The pregnancy outcomes after kidney transplantation were favorable and the mean birth body weight was 2208.8 ± 678.8 g at 35.4 ± 3.2 weeks gestational age. However, the maternal and neonatal complication rates were still high, such as preterm labor, preeclampsia, and small for gestational age.

A literature search reveals no studies concerning simultaneous identification of commonly abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry (LC–MS/MS). We developed and validated an LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine from suspected drug abusers. The instrument was operated in multiple-reaction monitoring using an electrospray ionization mode. Chromatograms were separated using an ACE5 C18 column on a gradient of acetonitrile. After liquid–liquid extraction, samples were passed through a 0.22-μm polyvinylidene difluoride filter before injection into the LC–MS/MS. The limits of quantitation ranged from 0.5 ng/mL to 31.3 ng/mL. The linearity ranged from 0.5 ng/mL to 200 ng/mL. The precision results were below 15.4% (intraday) and 18.7% (interday). The intraday accuracy ranged from 85.9% to 121.0%; interday accuracy ranged from 66.1% to 128.7%. The proposed method was applied to 769 urine samples. The most common three drugs identified were ketamine, amphetamine, and opiates. The drug positive rate for one or more drugs was 79.6%. Our results demonstrate the suitability of the LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine.

Objectives: Pleasant and humane childbirth is every mother's wish. We established one practicable and tailored Taiwanese mother-friendly childbirth model, and the objective of this study was to investigate the implementation, pregnancy outcomes, and women's satisfaction. Materials and methods: We used the Taiwanese mother-friendly childbirth model. Women from eight hospitals were divided into an experimental group and control group. The experimental group received prenatal care modified by the Taiwanese mother-friendly childbirth model and the control group received routine prenatal care according to their hospital. We performed a quasi-experimental study of women's satisfaction toward this mother-friendly childbirth model by questionnaires and surveyed the practicality and effectiveness of this model. Results: Seven hundred and fifty-one women from eight hospitals, including three medical centers and five regional hospitals were included. There was significantly different practices between the two groups, such as: (1) intermittent fetal monitoring for low-risk pregnancy; (2) no routine enema; (3) no perineal shaving; (4) less routine parenteral fluid support; (5) using an upright position; and (6) restrictive episiotomy. The mean maternal height, body weight gain, gestational age, birth weight, and episiotomy wound infection rate were indifferent. The epidural anesthesia rate and induction medication use were significantly lower in the experimental group. The self-reported pain score was higher in the experimental group and the self-reported satisfactory score was also higher in the experimental group, without statistical significance. Conclusion: Women receiving standardized prenatal care modified by the woman-friendly childbirth model of prenatal care had less epidural anesthesia, less induction medication, higher self-reported satisfaction score, and indifferent pregnancy outcomes such as gestational age, birth weight, and wound infection rate.

Objective: Pleasant and humane childbirth is every mother's wish. The objective of this study was to propose a practicable mother-friendly childbirth model tailored to Taiwanese women in order to improve the quality of perinatal care and maternal satisfaction. Material and methods: In this study, the guidelines of several countries were systematically reviewed, and a standard set of clinical guidelines were established by a focus group. In addition, a total of 172 Taiwanese obstetricians were visited, and a cross-sectional study of these obstetricians' attitudes toward the practicality and effectiveness of the model was performed using questionnaires. Results: A total of 10 suggestions were developed for this woman-friendly childbirth model, including: (1) intermittent fetal monitoring for low-risk pregnancy, (2) no routine enema, (3) no routine perineal shaving, (4) no routine restricted oral intake, (5) no routine parenteral fluid support, (6) no routine elective amniotomy, (7) nonpharmacological pain management, (8) upright position during childbirth, (9) delayed pushing, and (10) restrictive episiotomy. Taiwanese obstetricians approved of no routine oral intake restriction and providing nonmedical pain relief. The majority of obstetricians disagreed that perineal shaving and routine elective amniotomy were necessary, and agreed to modify their practice according to the suggestions. Suggestions were still being debated, such as no routine parenteral fluid support, using an upright position for childbirth, and delayed pushing. Intermittent fetal monitoring for low-risk pregnancy, no routine enema, and restrictive episiotomy were questioned by many Taiwanese obstetricians. Conclusion: Several suggestions were made in this model. However, there was still no consensus of Taiwanese obstetricians. More evidence for the advantages and disadvantages of the various suggestions was needed to convince Taiwanese obstetrician to modify their routine practice.

Objective: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy, which is also associated with future metabolic diseases in both patients and their offspring. The mechanisms underlying this condition remain largely unknown and may be partly related to epigenetics. The aim of this study was to compare the methylation levels of the cytokine interleukin-10 (IL-10) in pregnant women and their fetuses under both hyperglycemic and euglycemic environments, as those levels may be a clue to the epigenetic mechanisms underlying pathogenesis of GDM.Methods: We analyzed the methylation levels of the IL-10 gene in maternal blood, cord blood, and placental tissue in both a GDM group (n = 8) and a control group (n = 24) using a LightCycler LC480 (Roche, Rotkreuz, Switzerland). IL-10 concentrations in maternal blood and THP-1 cells were measured by enzyme-linked immunosorbent assay (ELISA) using BD OptEIA Human IL-10 ELISA kits (BD Biosciences Pharmingen, San Diego, CA, United States).Results: The maternal blood IL-10 methylation levels in the GDM group and the control group were 0.23 ± 0.04 and 0.26 ± 0.04, respectively (p = 0.03), but there were no significant differences between the levels of the two groups in the cord blood or placental tissue. Increased IL-10 plasma concentrations were discovered under hyperglycemic environments and were confirmed via the THP-1 cell line.Conclusion: Hypomethylation of maternal blood and increased plasma IL-10 concentrations before birth were found in the GDM group.

A cesarean section pregnancy (CSP) indicated the gestational sac (GS) implanted in the previous cesarean scar. The clinical manifestations of CSP present a wide range of variations, and the optimal management is yet to be defined. We retrospectively enrolled 109 patients with the diagnosis of CSP from our department and categorized them into four grades based on the ultrasound presentation. Grade I CSP indicated the GS embedded in less than one-half thickness of the lower anterior corpus; and grade II CSP represented the GS extended to more than one-half thickness of overlying myometrium. Grade III CSP implied the GS bulged out of the cesarean scar; and grade IV CSP denoted that GS became an amorphous tumor with rich vascularity at the cesarean scar. Seventy-eight women received surgery, and the complication rate was 14.1% (11/78). Linear regression analysis demonstrated a significant association between the invasiveness of the surgery and their ultrasound gradings. The mainstream operation for grade I CSP was transcervical resection, while the majority of grade III and IV patients required hysterotomy or hysterectomy. Another 31 women received chemotherapy with methotrexate as their initial treatment. The success rate for chemotherapy was 61.3%; the remaining patients required further surgery due to persistent CSP or heavy bleeding during or after chemotherapy. Fifteen patients (48.3%) receiving chemotherapy suffered from complications (mostly bleeding). Among them, 7 (22.6%) patients experienced bleeding of more than 1,000 mL, and 9 (29.0%) of these 31 patients required blood transfusions. Our novel ultrasound grading system for CSP may help to communicate between physicians, and determine the optimal surgical strategy. Chemotherapy with methotrexate for CSP is not satisfactory and is associated with a higher rate of complications.

OBJECTIVE:Using a specific cutoff of fasting plasma glucose (FPG) to screen gestational diabetes mellitus (GDM) can reduce the use of oral glucose tolerance tests (OGTT). Since the prevalence of GDM increases with age, this screening method may not be appropriate in healthcare systems where women become pregnant at older ages. Therefore, we aimed to develop a screening algorithm for GDM that takes maternal age into consideration. METHODS:We included 945 pregnant women without history of GDM who received 75g OGTT to diagnose GDM in 2011. Screening algorithms using FPG with or without age were developed. Another 362 pregnant women were recruited in 2013-2015 as the validation cohort. RESULTS:Using FPG criteria alone, more GDM diagnoses were missed in women ≥35 years than in women

Objective: To report five cases of major congenital malformations associated with common aneuploidies detected by rapid aneuploidy diagnosis. Case Reports: The fetus in the first case presented cebocephaly, semilobar holoprosencephaly, and tetralogy of Fallot on ultrasound at 25 gestational weeks. Cordocentesis using multiplex ligation-dependent probe amplification to detect aneuploidies of chromosomes X, Y, 13, 18, and 21 in uncultured cord blood revealed three copies of all targets on chromosome 13 consistent with the diagnosis of trisomy 13. The fetus in the second case presented bilateral choroid plexus cysts, congenital diaphragmatic hernia, and club foot on ultrasound at 18 gestational weeks. Amniocentesis using array-based comparative genomic hybridization (aCGH) in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 18 consistent with the diagnosis of trisomy 18. The fetus in the third case presented aortic stenosis and nuchal edema on ultrasound at 22 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a result of monosomy X and Turner syndrome. The fetus in the fourth case presented nuchal cystic hygroma and ventriculomegaly on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 21 consistent with the diagnosis of trisomy 21. The fetus in the fifth case presented holoprosencephaly, omphalocele, and hydronephrosis on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 13 consistent with the diagnosis of trisomy 13. Conclusions: Prenatal diagnosis of major congenital malformations should alert one to the possibility of chromosomal abnormalities. Multiplex ligation-dependent probe amplification and aCGH have the advantage of rapid aneuploidy diagnosis of common aneuploidies in cases with major congenital malformations.

Objective: Preimplantation genetic diagnosis (PGD) offers an alternative for women to carry an unaffected fetus risk of hereditary diseases. Trophectoderm biopsy may provide more cells for accurate diagnosis. However, the time allowed for transportation of the specimens to the laboratory and performance of molecular diagnosis is limited. We designed a PGD program of trophectoderm biopsy, vitrification of blastocysts, whole genome amplification (WGA), double confirmatory genotypings, and thawed embryo transfer. Case Report: We conducted this strategy for a woman of familial neurofibromatosis type I (NF-1). She had a genotype of heterozygous c.6709C>T mutation of NF1 gene. Trophectoderm biopsies were performed on 13 blastocysts. Then, individual blastocyst was vitrified. WGA was performed for the samples, followed by genotypings with both real-time polymerase chain reaction and sequencing. Eight embryos were diagnosed as unaffected, four were affected, and one was inconclusive because of allele drop-out. In the next cycle, two unaffected blastocysts were thawed and transferred, that resulted in a singleton pregnancy. The pregnancy was confirmed as unaffected by means of chorionic villi sampling. Conclusion: We first demonstrate successful application of blastocyst biopsy, vitrification, WGA, and thawed embryo transfer for PGD of a monogenic disease. Vitrification of blastocysts after biopsy permits sufficient time for shipment of samples and operation of molecular diagnosis.

Objective: Intact amniotic membranes may serve to protect the extremely fragile preterm infant from some of the mechanical forces caused by strong uterine contraction. This article introduces the technique of “en caul” cesarean delivery and reviews the experience of the National Taiwan University Hospital. Materials and Methods: This is a prospective study carried out to perform the “en caul” cesarean delivery for early preterm labors between October 2007 and December 2008. Cases were included if the estimated birth weight was below 1,500 g or gestational age was = 32 weeks. Results: Twenty women including four twin pregnancies were included, and 23 neonates were born with intact membranes. Preterm labor was indicated in 16 cases, and nine of the cases were due to severe hypertensive disorders during pregnancy. Except in the case of placenta accreta, all underwent lower transverse uterine incision without wound extension. One fetus died after 3 days due to sepsis and the mortality rate was 4.3%. A total of 15 babies had an Apgar score at 5 minutes of more than seven. The value of first arterial pH was 7.278 ± 0.117 and hemoglobin was 16.1 ± 2.1 g/dL. The corrected post-menstrual age at discharge was 277.75 ± 38.56 days. Conclusion: Cesarean delivery en caul is an effective and easy technique for extremely preterm fetuses to protect them from pressure trauma and also results in less uterine injury.

Objective: To assess the usefulness of quadruple test screening for Down syndrome in Taiwan. Materials and Methods: Maternal serum concentrations of a-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured in 21,481 pregnant women from 15 to 20 weeks of gestation. Results: Of the 21,481 women, 977 returned values greater than the high-risk cut-off value (1 in 270). Most of these women (86.2%) decided to have an invasive procedure for genetic diagnosis. Nine cases of Down syndrome and 19 cases of other chromosomal anomalies were detected prenatally. Two children with Down syndrome were diagnosed after delivery even though a low estimated risk was determined following the quadruple test. The detection rate was 81.8% (nine out of 11 cases), with a 4.4% false-positive rate. The median multiple of the median value for a-fetoprotein, human chorionic gonadotropin, unconjugated estriol and inhibin A were 0.87, 2.34, 0.77 and 2.16, respectively, in affected cases. Conclusion: This is the first study of the quadruple test for Down syndrome in a Chinese population. Our findings suggested that the second-trimester quadruple test provides an effective screening tool for Down syndrome in Taiwan.

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.

Objective: To present intensive intrauterine treatment of recurrent early onset fetal erythroblastosis due to anti-M alloimmunization. Case Report: A 33-year-old woman, gravid 3, para 1, had anti-M IgG antibody, which caused alloimmunization of her previous pregnancies. This time she visited our hospital for intensive intervention. No evidence of fetal hydrops was found during ultrasound examination at 12 weeks of gestation. Plasmapheresis was given from 17 weeks of gestation but fetal erythroblastosis still developed 1 week later. Two intraperitoneal transfusions and one intracardiac transfusion were given within three days but fetal erythroblastosis still progressed to fetal bradycardia and occasional asystole. Epinephrine resuscitation could only temporarily improve the fetal heart rate and fetal death was inevitable. Conclusion: Serial measurements of fetal middle cerebral artery peak systolic velocities, advanced plasmapheresis, intrauterine blood transfusion, and, if needed, intravenous immunoglobulin supplement, may be the appropriate treatment for early onset fetal erythroblastosis resulting from alloimmunization.

Objective: Laminaria placement is seldom thought to be associated with postabortal sepsis Case Report: A nulliparous woman presented with high fever, low blood pressure, and signs of infection during artificial legal abortion with laminaria placement for cervical dilatation. Broad-spectrum antibiotics were given. Cultures of blood, placenta, and arterial line all yielded Enterobacter cloacae. The patient responded to antibiotics and supportive care. Conclusion: The use of laminaria still places patients at risk for infection because there is a certain risk of ascending colonization with potentially pathogenic microorganisms from the vaginal and cervical microflora, as in our patient. Surgical disinfection, prophylactic antibiotics, and shortened duration of laminaria placement are helpful to prevent infectious insult. Once signs of infection are noted, physicians should take action as soon as possible, such as initiating broad-spectrum antibiotics and intensive care.

There are little data about adverse effects and immunogenicity of flu vaccine in Asian pregnant women.This prospective trial (NCT01514708) enrolled 46 pregnant women who received a single intramuscular dose of trivalent flu vaccine (AdimFlu-S®) containing 15 mcg of hemagglutinin for each strain/0.5 mL from influenza A (H1N1), influenza A (H3N2), and influenza B after the first trimester. Blood samples were collected at day 0 and 28 after vaccination, and at delivery. Cord blood was also collected. Hemagglutination inhibition (HAI) assays were performed to determine seroprotection and seroconversion rates and fold increase in the HAI geometric mean titer (GMT).Twenty-eight days after vaccination the seroprotection rate against H1N1, H3N2, and influenza B was 91.3%, 84.8% and 56.5%, respectively. The GMT fold increase was 12.8, 8.4, and 4.6 for H1N1, H3N2, and influenza B, respectively. At delivery, both the seroprotection rate (86.4%, 68.2%, and 47.7%) and GMT fold increase (9.4, 5.7 and 3.8) were slightly lower than day 28. The seroprotection rate and GMT fold increase in maternal and cord blood samples were comparable. No significant adverse effects were detected.Trivalent flu vaccine induces a strong immune response in pregnant women and their infants without adverse effects.Clinical Trials. gov NCT01514708.

Phytochelatin synthase (PCS) uses the substrates glutathione (GSH, γGlu-Cys-Gly) and a cadmium (Cd)-bound GSH (Cd∙GS2) to produce the shortest phytochelatin product (PC2, (γGlu-Cys)2-Gly) through a ping-pong mechanism. The binding of the 2 substrates to the active site, particularly the second substrate binding site, is not well-understood. In this study, we generated a structural model of the catalytic domain of Arabidopsis AtPCS1 (residues 12-218) by using the crystal structure of the γGlu-Cys acyl-enzyme complex of the PCS of the cyanobacterium Nostoc (NsPCS) as a template. The modeled AtPCS1 revealed a cavity in proximity to the first substrate binding site, consisting of 3 loops containing several conserved amino acids including Arg152, Lys185, and Tyr55. Substitutions of these amino acids (R152K, K185R, or double mutation) resulted in the abrogation of enzyme activity, indicating that the arrangement of these 2 positive charges is crucial for the binding of the second substrate. Recombinant AtPCS1s with mutations at Tyr55 showed lower catalytic activities because of reduced affinity (3-fold for Y55W) for the Cd∙GS2, further suggesting the role of the cation-π interaction in recognition of the second substrate. Our study results indicate the mechanism for second substrate recognition in PCS. The integrated catalytic mechanism of PCS is further discussed.

A retrospective analysis of the Taiwanese National Birth Defect Registration and Notification System was conducted in order to determine the live birth- and stillbirth rates in infants with Down syndrome, trisomy 18, trisomy 13 and Turner syndrome between 2001 and 2010. The objective was to investigate the impact of Down syndrome screening on the Taiwanese Down syndrome live birth rate. In addition, the results of first-trimester Down syndrome screening between 2006 and 2011, and of second-trimester quadruple testing between 2008 and 2011, were obtained from the National Taiwan University Hospital. All Taiwanese infants born between 2001 and 2010 were included in the first part of the analysis, and women receiving first-trimester Down syndrome screening or second-trimester quadruple testing from the National Taiwan University Hospital were included in the second part. The live birth rate of infants with Down syndrome, per 100 000 live births, decreased from 22.28 in 2001 to 7.79 in 2010. The ratio of liveborn DS to total DS was 48.74% in 2001, and then decreased to 25.88% in 2006, when first-trimester screening was widely introduced in Taiwan. This ratio dropped to 20.64% in 2008, when the second-trimester quadruple test was implemented. The overall positive rate in first-trimester screening in the National Taiwan University Hospital was 3.1%, with a Down syndrome detection rate of 100%; the quadruple test had values of 9.0% and 75%, respectively. The use of first-trimester screening and the second-trimester quadruple test may be responsible for the marked decrease in the Taiwanese Down syndrome live birth rate observed between 2001 and 2010.

BackgroundSpinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program.Methods and findingsThis is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968.ConclusionThe main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling.

Universal newborn hearing screening (UNHS) is of paramount importance for early identification and management of hearing impairment in children. However, infants with slight/mild, progressive, or late-onset hearing impairment might be missed in conventional UNHS. To investigate whether genetic screening for common deafness-associated mutations could assist in identifying these infants, 1017 consecutive newborns in a tertiary hospital were subjected to both newborn hearing screening using a two-step distortion-product otoacoustic emissions (DPOAE) screening and newborn genetic screening (NGS) for deafness. The NGS targeted 4 deafness-associated mutations commonly found in the Taiwanese population, including p.V37I (c.109G>A) and c.235delC of the GJB2 gene, c.919-2A>G of the SLC26A4 gene, and mitochondrial m.1555A>G of the 12S rRNA gene. The results of the NGS were then correlated to the results of the NHS. Of the 1017 newborns, 16 (1.6%) had unilateral DPOAE screening failure, and 22 (2.2%) had bilateral DPOAE screening failure. A total of 199 (19.6%) babies were found to have at least 1 mutated allele on the NGS for deafness, 11 (1.1%) of whom were homozygous for GJB2 p.V37I, 6 (0.6%) compound heterozygous for GJB2 p.V37I and c.235delC, and 1 (0.1%) homoplasmic for m.1555A>G, who may potentially have hearing loss. Among them, 3 babies, 5 babies, and 1 baby, respectively, passed the NHS at birth. Comprehensive audiological assessments in the 9 babies at 3 months identified 1 with slight hearing loss and 2 with mild hearing loss. NGS for common deafness-associated mutations may identify infants with slight/mild or potentially progressive hearing impairment, thus compensating for the inherent limitations of the conventional UNHS.

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life. [ABSTRACT FROM AUTHOR]