Fast inflows as the adjacent fuel of supermassive black hole accretion disks in quasars.

Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.

Exploring factors impacting haplotype-based noninvasive prenatal diagnosis for single-gene recessive disorders.

Haplotype-based noninvasive prenatal diagnosis (NIPD) is applicable for various recessive single-gene disorders in proband families. However, a comprehensive exploration of critical factors influencing the assay performance, such as fetal fraction, informative single nucleotide polymorphism (SNP) count, and recombination events, has yet to be performed. It is critical to identify key factors affecting NIPD performance, including its accuracy and success rate, and their impact on clinical diagnostics to guide clinical practice. We conducted a prospective study, recruiting 219 proband families with singleton pregnancies at risk for eight recessive single-gene disorders (Duchenne muscular dystrophy, spinal muscular atrophy, phenylketonuria, methylmalonic acidemia, hemophilia A, hemophilia B, non-syndromic hearing loss, and congenital adrenal hyperplasia) at 7-14 weeks of gestation. Haplotype-based NIPD was performed by evaluating the relative haplotype dosage (RHDO) in maternal circulation, and the results were validated via invasive prenatal diagnosis or newborn follow-ups. Among the 219 families, the median gestational age at first blood draw was 8+5 weeks. Initial testing succeeded for 190 families and failed for 29 due to low fetal fraction (16), insufficient informative SNPs (9), and homologous recombination near pathogenic variation (4). Among low fetal fraction families, successful testing was achieved for 11 cases after a redraw, while 5 remained inconclusive. Test failures linked to insufficient informative SNPs correlated with linkage disequilibrium near the genes, with F8 and MMUT exhibiting the highest associated failure rates (14.3% and 25%, respectively). Homologous recombination was relatively frequent around the DMD and SMN1 genes (8.8% and 4.8%, respectively) but led to detection failure in only 44.4% (4/9) of such cases. All NIPD results from the 201 successful families were consistent with invasive diagnostic findings or newborn follow-up. Fetal fraction, informative SNPs count, and homologous recombination are pivotal to NIPD performance. Redrawing blood effectively improves the success rate for low fetal fraction samples. However, informative SNPs count and homologous recombination rates vary significantly across genes, necessitating careful consideration in clinical practice. We have designed an in silico method based on linkage disequilibrium data to predict the number of informative SNPs. This can identify genomic regions where there might be an insufficient number of SNPs, thereby guiding panel design. With these factors properly accounted for, NIPD is highly accurate and reliable.

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction.

Fetal growth restriction (FGR) is associated with increased susceptibility to perinatal morbidity and mortality. Evidence suggests that epigenetic changes play critical roles in the regulation of fetal growth. We sought to present a comprehensive analysis of the associations between placental DNA methylation and selective fetal growth restriction (sFGR), which is a severe complication of monochorionic twin pregnancies, characterized by one fetus experiencing restricted growth. Genome-wide methylation analysis was performed on 24 placental samples obtained from 12 monochorionic twins with sFGR (Cohort 1) using Illumina Infinium MethylationEPIC BeadChip. Integrative analysis of our EPIC data and two previous placental methylation studies of sFGR (a total of 30 placental samples from 15 sFGR twins) was used to identify convincing differential promoter methylation. Validation analysis was performed on the placentas from 15 sFGR twins (30 placental samples), 15 FGR singletons, and 14 control singletons (Cohort 2) using pyrosequencing, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry (IHC). A globe shift toward hypomethylation was identified in the placentas of growth-restricted fetuses compared with the placentas of normal fetuses in monochorionic twins, including 5625 hypomethylated CpGs and 452 hypermethylated CpGs, especially in the regions of CpG islands, gene-body and promoters. The analysis of pathways revealed dysregulation primarily in steroid hormone biosynthesis, metabolism, cell adhesion, signaling transduction, and immune response. Integrative analysis revealed a differentially methylated promoter region in the CYP11A1 gene, encoding a rate-limiting enzyme of steroidogenesis converting cholesterol to pregnenolone. The CYP11A1 gene was validated to have hypomethylation and higher mRNA expression in sFGR twins and FGR singletons. In conclusion, our findings suggested that the changes in placental DNA methylation pattern in sFGR may have functional implications for differentially methylated genes and regulatory regions. The study provides reliable evidence for identifying abnormally methylated CYP11A1 gene in the placenta of sFGR.

First-trimester noninvasive prenatal diagnosis of seven facioscapulohumeral muscular dystrophy type 1 families using SNP-based amplicon sequencing: An earlier, rapid and safer way.

The study is to explore the feasibility and value of SNP-based noninvasive prenatal diagnosis (NIPD) for facioscapulohumeral muscular dystrophy type 1 (FSHD1) in early pregnancy weeks. We prospectively collected seven FSHD1 families, with an average gestational age of 8+6. Among these seven couples, there were three affected FSHD1 mothers and four affected fathers. A multiplex-PCR panel comprising 402 amplicons was designed to selective enrich for highly heterozygous SNPs upstream of the DUX4 gene. Risk haplotype was constructed based on familial linkage analysis. Fetal genotypes were accurately inferred through relative haplotype dosage analysis using Bayes Factor. All tests were successfully completed in a single attempt, and no recombination events were detected. NIPD results were provided within a week, which is 4 weeks earlier than karyomapping and 7 weeks earlier than Bionano single-molecule optical mapping (BOM). Ultimately, five FSHD1 fetuses and two normal fetuses were successfully identified, with a 100% concordance rate with karyomapping and BOM. Therefore, SNP-based NIPD for FSHD1 was demonstrated to be feasible and accurate in early weeks of gestation, although the risk of recombination events cannot be completely eliminated. In the future, testing of more cases is still necessary to fully determine the clinical utility.

Noninvasive twin genotyping for recessive monogenic disorders by relative haplotype dosage.

OBJECTIVE: To establish a haplotype-based noninvasive prenatal testing (NIPT) workflow for single-gene recessive disorders that adapt to dizygotic (DZ) twin pregnancies. METHOD: Twin pregnancies at risk of Duchenne muscular dystrophy, Becker muscular dystrophy, hemophilia B, spinal muscular atrophy, phenylketonuria, and nonsyndromic hearing loss were recruited. For subsequent analysis, capture sequencing targeting highly heterozygotic single nucleotide polymorphism sites was conducted. Paternal-specific alleles were used to calculate the total and individual fetal fractions and determine zygosity. A two-step Bayes Factor model was applied to clarify the complex genomic landscape in the maternal plasma: the first step involved determining whether the twins inherited the same haplotype, and the second step involved estimating their individual genotypes. NIPT results were subsequently confirmed by invasive diagnosis. RESULTS: Nine twin pregnancies were recruited, including five DZ and four monozygotic (MZ) twins. The earliest gestational age was 8+0 weeks, and the minimum fetal fraction was 4.6%. Three twin pregnancies were reported with one affected fetus, while the remaining six were reported without affected fetuses. Two dichorionic diamniotic twin pregnancies were confirmed to be MZ twins. The NIPT results were 100% consistent with those of invasive procedures or diagnostic genetic testing after birth. CONCLUSION: This study is the first to perform NIPT for single-gene disorders in twin pregnancies and preliminarily confirm its clinical feasibility. Acknowledging the twins' genotypes in the first trimester is valuable as it empowers obstetric care providers and parents to have adequate time for pregnancy management and decision-making.

[Expert consensus on the test development and preliminary implementation of whole genome sequencing for fetal structural abnormalities].

Fetal structural anomalies and birth defects are primarily caused by genetic variants such as chromosomal number abnormalities, copy number variations (CNV), single nucleotide variants (SNV), and small insertions and deletions (indel). Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) as an emerging technology for genetic disease diagnosis can detect the aforementioned types of variants. In recent years, high-depth WGS (> 30×) for prenatal diagnosis has also become available, and proved to be practical for unraveling the genetic etiology of fetal developmental abnormalities. To facilitate clinical practice, test development and preliminary implementation of WGS for diagnosing fetal structural anomalies, we have formulated a consensus over the application of WGS in prenatal diagnosis by compiling previously published consensuses, guidelines, and research findings to provide a guidance on data analysis, reporting recommendations, and consultation of prenatal WGS results.

Chromosomal abnormalities in recurrent pregnancy loss and its association with clinical characteristics.

OBJECTIVE: To evaluate the distribution of chromosomal abnormalities in a recurrent pregnancy loss (RPL) cohort and explore the associations between chromosomal abnormalities and clinical characteristics. METHOD: Over a 5-year period, fresh products of conception (POC) from women with RPL were analyzed by single-nucleotide polymorphism (SNP) array at our hospital. After obtaining the information on clinical characteristics, we investigated the associations between the causative chromosomal abnormalities and clinical characteristics by the chi-squared test or Fisher's exact test and logistic regression. RESULTS: A total of 2383 cases were enrolled. Overall, 56.9% (1355/2383) were identified with causative chromosomal abnormalities, of which 92.1% (1248/1355) were numerical abnormalities, 7.5% (102/1355) were structural variants, and 0.4% (5/1355) were loss of heterozygosity (LOH). The risk of numerical abnormalities was increased in women with maternal age ≥ 35 years (OR, 1.71; 95% CI, 1.41-2.07), gestational age at pregnancy loss ≤ 12 weeks (OR, 2.78; 95% CI, 1.79-4.33), less number of previous pregnancy losses (twice: OR, 2.32; 95% CI, 1.84-2.94; 3 times: OR, 1.59; 95% CI, 1.23-2.05, respectively), and pregnancy with a female fetus (OR, 1.37; 95% CI, 1.15-1.62). The OR of pregnancy loss with recurrent abnormal CMA was 4.00 (95% CI: 1.87-8.58, P < 0.001) and the adjusted OR was 5.05 (95% CI: 2.00-12.72, P = 0.001). However, the mode of conception was not associated with the incidence of numerical abnormality. No association was noted between structural variants and clinical characteristics. CONCLUSION: Chromosomal abnormality was the leading cause of RPL. Numerical chromosome abnormality was more likely to occur in cases with advanced maternal age, an earlier gestational age, fewer previous pregnancy losses, and pregnancy with a female fetus.

Intertwin Membrane Perforation and Umbilical Cord Entanglement after Laser Surgery for Twin-Twin Transfusion Syndrome: Prevalence, Risk Factors, and Outcome.

INTRODUCTION: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of subsequent cord entanglement are limited. The objective of this study was to assess the prevalence, risk factors and outcome of intertwin membrane perforation, and cord entanglement after laser surgery for TTTS. METHODS: In this multicenter retrospective study, we included all TTTS pregnancies treated with laser surgery in two fetal therapy centers, Shanghai (China) and Leiden (the Netherlands) between 2002 and 2020. We evaluated the occurrence of intertwin membrane perforation and cord entanglement after laser, based on routine fortnightly ultrasound examination and investigated the risk factors and the association with adverse short- and long-term outcomes. RESULTS: Perforation of the intertwin membrane occurred in 118 (16%) of the 761 TTTS pregnancies treated with laser surgery and was followed by cord entanglement in 21% (25/118). Perforation of the intertwin membrane was associated with higher laser power settings, 45.8 Watt versus 42.2 Watt (p = 0.029) and a second fetal surgery procedure 17% versus 6% (p < 0.001). The group with intertwin membrane perforation had a higher rate of caesarean section (77% vs. 31%, p < 0.001) and a lower gestational age at birth (30.7 vs. 33.3 weeks of gestation, p < 0.001) compared to the group with an intact intertwin membrane. Severe cerebral injury occurred more often in the group with intertwin membrane perforation, 9% (17/185) versus 5% (42/930), respectively (p = 0.019). Neurodevelopmental outcome at 2 years of age was similar between the groups with and without perforation of the intertwin membrane and between the subgroups with and without cord entanglement. CONCLUSION: Perforation of the intertwin membrane after laser occurred in 16% of TTTS cases treated with laser and led to cord entanglement in at least 1 in 5 cases. Intertwin membrane perforation was associated with a lower gestational age at birth and a higher rate of severe cerebral injury in surviving neonates.

[Free sialic acid storage disorders with fetal hydrops in a neonate]. / å”¾æ¶²é ¸è´®ç§¯ç—‡ä¼´èƒŽå„¿æ°´è‚¿1例.

A boy, aged 3 hours, was admitted due to a prenatal diagnosis of fetal hydrops at 3 hours after resuscitation for birth asphyxia. Prenatal examination at 5 months of gestation showed massive ascites in the fetus, and after birth, the boy had the manifestations of systemic hydroderma, massive ascites, coarse face, and hepatomegaly. Genetic testing revealed heterozygous mutations in the SLC17A5 gene, and there was a significant increase in urinary free sialic acid. Placental pathology showed extensive vacuolization in villous stromal cells, Hofbauer cells, cytotrophoblast cells, and syncytiotrophoblast cells in human placental chorionic villi. The boy was finally diagnosed with free sialic acid storage disorders (FSASDs). This is the first case of FSASDs with the initial symptom of fetal hydrops reported in China. The possibility of FSASDs should be considered for cases with non-immune hydrops fetalis, and examinations such as placental pathology and urinary free sialic acid may help with early diagnosis and clinical decision making.

Selective reduction in complicated monochorionic pregnancies: a systematic review and meta-analysis of different techniques.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the perinatal outcomes of complicated monochorionic pregnancies after selective reduction by radiofrequency ablation, bipolar cord coagulation, and interstitial laser. DATA SOURCES: We searched PubMed, Scopus, and Web of Science, from the inception of the database up to April 26, 2021. STUDY ELIGIBILITY CRITERIA: Studies comparing at least 2 selective reduction techniques among complicated monochorionic pregnancies and presenting data on perinatal outcomes, including gestational age at procedure, gestational age at delivery, procedure to delivery interval, preterm premature rupture of membranes, preterm birth, survival rate, and birthweight, were eligible. METHODS: The random-effects model was used to pool the mean differences or odds ratios and corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 10 studies with 734 cases of fetal reduction met the inclusion criteria, of which 9 studies with 674 fetuses were eligible for quantitative synthesis. In 8 studies that compared radiofrequency ablation with bipolar cord coagulation, radiofrequency ablation was associated with increased procedure to delivery interval (days) (mean difference, 13.42; 95% confidence interval, 1.90-24.94; P=.02; I2=0.0%), decreased preterm birth (odds ratio, 0.50; 95% confidence interval, 0.29-0.85; P=.01; I2=3.0%), and decreased preterm premature rupture of membranes (odds ratio, 0.45; 95% confidence interval, 0.27-0.73; P=.001; I2=0.0%). Radiofrequency ablation and bipolar cord coagulation had comparable survival rates (odds ratio, 0.85; 95% confidence interval, 0.54-1.35; P=.49; I2=0.0%). In 3 studies that compared radiofrequency ablation with interstitial laser, there was no significant difference in gestational age at delivery (P=.07) or survival (P=.15). In 3 studies that compared bipolar cord coagulation with interstitial laser, bipolar cord coagulation was associated with a higher survival rate (odds ratio, 3.21; 95% confidence interval, 1.13-9.10; P=.03; I2=0.0%), but the gestational age at delivery was comparable between groups (P=.16). CONCLUSION: This study demonstrated that radiofrequency ablation has a greater procedure to delivery interval and decreased preterm premature rupture of membranes and preterm birth than bipolar cord coagulation. Although there was no difference in gestational age at delivery for either bipolar cord coagulation, radiofrequency ablation, or interstitial laser, survival was higher with bipolar cord coagulation than with interstitial laser.

Prenatal diagnosis for fetuses with isolated and non-isolated congenital heart defects using chromosomal microarray and exome sequencing.

OBJECTIVE: To investigate the use of chromosomal microarray (CMA) and Exome sequencing (ES) in fetuses with congenital heart disease (CHD). METHODS: The Fetal Medicine Unit of Shanghai First Maternity and Infant Hospital records were reviewed to ascertain all cases diagnosed with CHD by level 2 ultrasound examination between 2016 and 2019. Cases were categorized as isolated or associated with other abnormalities or fetal growth restriction. CMA was offered to all cases as a first-line genetic test followed by ES when CMA was non-diagnostic. RESULTS: Of the 586 ascertained, 84 (14.3%) had causative CMA abnormality, of which 8.8% (35/400) were in fetuses with isolated CHD and 26.3% (49/186) in those with other abnormalities. ES was performed in 47 cases with a negative CMA. Causative variants were identified in two (10.5%, 2/19) isolated cases and four(14.3%, 4/28) with other abnormalities. CONCLUSION: Invasive procedures with CMA should be offered in pregnancies complicated by both non-isolated and isolated cardiac abnormalities. When CMA is not diagnostic, ES can add diagnostic value in both groups and should be considered even for fetuses with an isolated CHD.

Noninvasive prenatal testing of Duchenne muscular dystrophy in a twin gestation.

PURPOSE: Haplotype-based assay has been proved efficient in noninvasive prenatal testing for various monogenic disorders in singleton pregnancies. However, its application in twin pregnancies is still blank. Here we provide a novel algorithmic approach to noninvasively assess fetal genotypes in a dizygotic twin pregnancy at risk for Duchenne muscular dystrophy (DMD). METHODS: One pregnant woman carrying a dizygotic twin gestation was recruited as she was a heterozygote of DMD gene duplication and has delivered an affected son. Construction of parental haplotypes was achieved by target sequencing of DNA samples from the parent and the proband. Single nucleotide polymorphisms within target regions were classified into six categories according to parental haplotypes. Individual fetal fractions were calculated using paternal heterozygous. Maternal-inherited haplotype was deduced using relative haplotype dosage through a two-step Bayesian model. RESULTS: One male fetus with a lower fetal fraction of 4.6% and one female fetus with a higher fetal fraction of 10.1% were observed. The male fetus was predicted to be a DMD pathogenic variant carrier, while the female fetus was predicted to be homozygous normal. Noninvasive prenatal testing (NIPT) results were concordant with the findings of invasive prenatal diagnosis. CONCLUSIONS: This study is the first report of the use of NIPT for the assessment of DMD in a twin pregnancy. The algorithm provided could expand the use of NIPT to monogenic disorders in dizygotic twin pregnancies.

Pregnancy Loss After Amniocentesis with Double-Needle Insertions in Twin Pregnancies.

The aim of this study was to determine the pregnancy loss rate of amniocentesis with double-needle insertions in twin pregnancies. This was a retrospective study of twin pregnancies who underwent amniocentesis with double-needle insertion between 2010 and 2019 at a single center. The pregnancy loss rates were recorded as single or double fetal loss before 24 weeks' gestation and within 4 weeks after the procedure. Risk factors for pregnancy loss after amniocentesis were also assessed. A total of 678 twin pregnancies with amniocentesis were finally included. The pregnancy loss rates before 24 weeks' gestation and within 4 weeks after the procedure were 0.9% and 1.9%, respectively. Only one fetal loss was presumed to be a direct result of the procedure. All other cases were complicated by structural or chromosomal anomalies. Twin pregnancies with abnormal ultrasound findings had a significantly higher rate of pregnancy loss with a relative risk of 4.81 (95% CI [1.03, 22.2]). Our study showed a low pregnancy loss rate after amniocentesis in twin pregnancies with double-needle insertions technique of sampling, which can help decision making in prenatal screening and diagnosis for twin pregnancies.

The Value of Exome Sequencing in Thoracoamniotic Shunt for Severe Pleural Effusion with Fetal Hydrops: A Retrospective Clinical Study.

OBJECTIVE: We aimed to study the value of exome sequencing (ES) in severe pleural effusion with nonimmune hydrops fetalis (NIHF) that underwent thoracoamniotic shunt (TAS). METHODS: It was a retrospective study of NIHF that underwent TAS between 2012 and 2020 at Shanghai First Maternity and Infant Hospital. After a detailed assessment, NIHF cases with aneuploidies, infections, and structural anomalies were excluded, and TAS was offered to cases with severe pleural effusion. Quantitative fluorescence polymerase chain reaction (QF-PCR) was conducted to exclude Trisomy 21, 18, and 13 before fetal therapy, and chromosomal microarray analysis (CMA) was offered to all the cases. Before 2019, ES was retrospectively performed using stored fetal DNA extracted from prenatal samples; from 2019 onward, ES was discussed and offered before intrauterine therapies. RESULTS: A total of 18 NIHF cases underwent TAS with negative CMA and continuing pregnancy were included. Fetal hydrops was relieved in 16 cases (88.9%). The median gestational ages at intervention and at delivery were 31.2 (22.0-33.1) weeks and 34.3 (29.7-38.6) weeks, respectively. The neonatal survival rate was 72.2% (13/18), and no causative gene variants were identified from ES in any survivors. Pathogenic or likely pathogenic variants were detected in 3 out of 5 neonatal deaths. If rapid ES could have been available to guide fetal therapy, the neonatal survival rate after TAS would have increased from 72.2% to 86.7%. CONCLUSIONS: Single-gene disorders were one of the major causes of perinatal death in NIHF cases that underwent fetal therapy. Prenatal rapid ES may be of good promise in NIHF to explore precise etiology and guide fetal therapy.

Fetal growth standards for Chinese twin pregnancies.

BACKGROUND: The common use of singleton fetal growth standard to access twin growth might lead to over-monitoring and treatment. We aimed to develop fetal growth standards for Chinese twins based on ultrasound measurements, and compare it with Zhang's and other twin fetal growth charts. METHODS: A cohort of uncomplicated twin pregnancies were prospectively followed in 2014-2017. Smoothed estimates of fetal growth percentiles for both monochorionic (MC) and dichorionic (DC) twins were obtained using a linear mixed model. We also created growth charts for twins using a model-based approach proposed by Zhang et al. Our twin standards were compared with Hadlock's (singleton) in predicting adverse perinatal outcomes. RESULTS: A total of 398 twin pregnancies were included, with 214 MC and 582 DC live-born twins. The MC twins were slightly lighter than the DC twins, with small differences throughout the gestation. Our ultrasound-based fetal weight standards were comparable to that using Zhang's method. Compared with previous references/standards from the US, Brazil, Italy and UK, our twins had very similar 50th percentiles, but narrower ranges between the 5th and 95th or 10th and 90th percentiles. Compared with the Hadlock's standard, the risks of neonatal death and adverse perinatal outcomes for small for gestational age (SGA) versus non-SGA were substantially elevated using our standards. CONCLUSIONS: A normal fetal growth standard for Chinese twins was created. The differences between MC and DC twins were clinically insignificant. The 50th weight percentiles of the Chinese twins were identical to those in other races/ethnicities but the ranges were markedly narrower. Our standard performed much better than the Hadlock's in predicting low birth weight infants associated with adverse perinatal outcomes in twin pregnancies. The present study also indicated that Zhang's method is applicable to Chinese twins, and other areas may use Zhang's method to generate their own curves for twins if deemed necessary.

Placental Abruption after Fetoscopic Laser Surgery in Twin-Twin Transfusion Syndrome: The Role of the Solomon Technique.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) is a complication in monochorionic twin pregnancies which is preferably treated with fetoscopic laser surgery. A few small studies suggested a possible association between the Solomon laser technique and placental abruption. METHODS: The objective of this study is to compare the rate of and to explore potential risk factors for placental abruption in TTTS treated with fetoscopic laser surgery according to the Selective and Solomon laser technique. We conducted a large retrospective cohort study of consecutive TTTS-cases treated with fetoscopic laser surgery in Shanghai, China, and Leiden, The Netherlands treated with either the Selective laser technique (Selective group) or Solomon laser technique (Solomon group). RESULTS: The rate of placental abruption in the Selective group versus the Solomon group was 1.7% (5/289) and 3.4% (15/441), respectively (p = 0.184). No risk factors for placental abruption were identified. Placental abruption was associated with lower gestational age at birth (p = 0.003) and severe cerebral injury (p = 0.003). CONCLUSION: The prevalence of placental abruption in TTTS after fetoscopic laser surgery is low, although it appears higher than in the overall population. Placental abruption is associated with a lower gestational age at birth, which is associated with severe cerebral injury. The rate of placental abruption was not significantly increased with the use of the Solomon technique. Continued research of placental abruption in TTTS is necessary to determine why the rate is higher than in the overall population.

Intrauterine phenotype features of fetuses with Williams-Beuren syndrome and literature review.

Williams-Beuren syndrome (WBS) is a well-defined multisystem chromosomal disorder that is caused by a chromosome 7q11.23 region heterozygous deletion. We explored prenatal diagnosis of WBS by ultrasound as well as multiple genetic methods to characterize the structural variants of WBS prenatally. Expanded noninvasive prenatal testing (NIPT-plus) was elected as a regular prenatal advanced screen for risk assessments of fetal chromosomal aneuploidy and genome-wide microdeletion/microduplication syndromes at the first trimester. At the second and three trimester, seven prenatal cases of WBS were evaluated for the indication of the invasive testing, the ultrasound features, cytogenetic, single-nucleotide polymorphism array (SNP array), and fluorescent quantitative PCR (QF-PCR) results. The NIPT-plus results for seven fetuses were low risk. All cryptic aberrations were detected by the SNP array as karyotyping analyses were negative. Subsequently, QF-PCR further confirmed the seven deletions. Combining our cases with 10 prenatal cases from the literature, the most common sonographic features were intrauterine growth retardation (82.35%, 14/17) and congenital cardiovascular abnormalities (58.82%, 10/17). The manifestations of cardiovascular defects mainly involve supravalvar aortic stenosis (40%, 4/10), ventricular septal defect (30%, 3/10), aortic coarctation (20%, 2/10), and peripheral pulmonary artery stenosis (20%, 2/10). To the best of our knowledge, this is the first largest prenatal study of WBS cases with detailed molecular analysis. Aortic coarctation combined with persistent left superior vena cava and right aortic arch cardiovascular defects were first reported in prenatal WBS cases by our study.

Screening for preeclampsia in low-risk twin pregnancies at early gestation.

INTRODUCTION: Preeclampsia affects about 10% of twin pregnancies and significantly increases the risk of adverse pregnancy outcomes. However, screening models for preeclampsia in twin pregnancies remain elusive. The present study aimed to evaluate the performance of a multi-marker first trimester preeclampsia screening model in low-risk twin pregnancies. MATERIAL AND METHODS: Between 2014 and 2017, we prospectively assessed first trimester biomarkers for preeclampsia in a 'low-risk' twin pregnancy cohort at a single center. Multiple logistic regression was used to determine significant predictors for early preeclampsia (occurring prior to 34 weeks) and late preeclampsia (occurring after 34 weeks). The performance of the screening models fitted using the significant predictors was calculated using receiver operating characteristics curves, and internal validation was performed using bootstrapping. RESULTS: A total of 769 twin pregnancies were included in the study. Early preeclampsia and late preeclampsia developed in 27 (3.5%) and 59 (7.7%) cases, respectively. Logistic regression analyses showed that maternal age, body mass index, mean artery pressure and placental growth factor were significant predictors for early preeclampsia. Maternal age, body mass index, mean artery pressure and pregnancy-associated plasma protein A were significant for late preeclampsia. Uterine artery pulsatility index was not predictive of either early or late preeclampsia. For the fitted screening model of early and late preeclampsia, the areas under receiver operating characteristics curves were 0.82 (95% confidence interval [CI] 0.76-0.88) and 0.66 (95% CI 0.59-0.73), which were expected to decrease to 0.77 and 0.60, respectively, based on bootstrapping; the positive predictive values were 10.2% and 12.5%; and the estimated detection rates were 40.7% and 22.0%, respectively, at a false-positive rate of 10%. CONCLUSIONS: A multi-marker screening model for preeclampsia in low-risk twin pregnancies, using a modified version of Fetal Medicine Foundation predictors in singletons, does not perform well. Uterine artery pulsatility index is of little value in screening for preeclampsia in low-risk twin pregnancies.

[Prenatal diagnosis for a pedigree affected with Wolf-Hirschhorn syndrome due to a subtle chromosomal translocation].

OBJECTIVE: To make molecular diagnosis of an infant affected with severe developmental delay and multiple birth defects, assisting prenatal diagnosis for the second pregnancy. METHODS: Standard G-banded karyotyping was performed for the fetus and his parents. Single nucleotide polymorphism array (SNP array) was used to detect submicroscopic chromosomal aberration. Fluorescence in situ hybridization (FISH) was employed to determine the parental origin of the aberration. RESULTS: Both the proband and the fetus harbored a 5.4 Mb distal 4p deletion and a 6.9 Mb distal 6q duplication. FISH confirmed that the mother has carried a balanced translocation involving 4p and 6q. CONCLUSION: The unbalanced chromosomal aberration in the proband and the fetus were both derived from the mother. Both patients showed a Wolf-Hirschhorn syndrom phenotype and partial phenotype of 6q trisomy. SNP array combined with FISH are essential for the detection of cryptic chromosomal aberrations which may be missed by coventional karyotyping analysis.

Risk factors for fetal death after radiofrequency ablation for complicated monochorionic twin pregnancies.

OBJECTIVE: Radiofrequency ablation (RFA) is a management alternative for complicated monochorionic twin pregnancies. The purpose of this study is to evaluate risk factors for fetal death after RFA. METHODS: An observational study was performed to document the perinatal outcomes of all cases undergoing fetal reduction using RFA from 2010 to 2016 at the Shanghai First Maternity and Infant Hospital. A multiple regression model was built to identify predictors of the death of the remaining fetus after RFA. RESULTS: A total of 183 patients treated with RFA for fetal reduction were analyzed, including 53 selective intrauterine growth restriction, 35 twin-twin transfusion syndrome, 36 dichorionic triamniotic triplets, 24 monochorionic twins discordant for fetal anomaly, and 35 twin reversed arterial perfusion. The prevalence of fetal death after RFA was 23% (43:183). The occurrence of fetal death after RFA was independently associated with more than 2 cycles of RFA coagulation (OR 3.46; 95% CI, 1.34-8.94; P = .01). CONCLUSION: More than 2 cycles of RFA coagulation is the only independent risk factors of fetal death after RFA.