Objective To report the performance of massively parallel sequencing (MPS) based prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from maternal plasma in a routine clinical setting in China. MethodThe MPS-based test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant women in 49 medical centers over 2 years. A total of 11 263 participants were recruited and the MPS-based test was performed in 11 105 pregnancies. Fetal outcome data were obtained after the expected date of confinement.Results One hundred ninety cases were classified as positive, including 143 cases of trisomy 21 and 47 cases of trisomy 18.With the karyotyping results and the feedback of fetal outcome data, we observed one false positive case of trisomy 21, one false positive case of trisomy 18 and no false negative cases, indicating 100% sensitivity and 99.96% specificity for the detection of trisomies 21 and 18.Conclusion Our large-scale multicenter study proved that the MPS-based test is of high sensitivity and specificity in

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Context-Late preterm births (LPTB, 34 0/7-36 6/7 weeks) account for a growing proportion of prematurity-associated short term morbidities, particularly respiratory, that require specialized care and prolonged neonatal hospital stays.Objective-To assess short-term respiratory morbidity in LPTB compared to term births in a contemporary cohort of deliveries in the United States.Design, Setting, and Participants-Retrospective collection of electronic data from 12 institutions (19 hospitals) across the United States on 233,844 deliveries between 2002 and 2008. Charts were abstracted for all neonates with respiratory compromise admitted to a neonatal intensive care unit (NICU) and LPTB were compared to term births in regard to resuscitation, respiratory support and respiratory diagnoses. A multivariate logistic regression analysis compared infants at each gestational week controlling for factors that influence respiratory outcomes.Corresponding Author: Judith U. Hibbard, MD, Address: University of Illinois at Chicago, 820 South Wood Street, department of Ob/ Gyn, M/C 808, Chicago, IL 60612, Phone Number: 312 996-7300, Fax Number: 312 996-4135, jhibbar@uic.edu. * The Consortium on Safe LaborAll authors contributed to the study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis, administrative, technical, or material support, and study supervision.Disclosures: All authors are without potential conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of this manuscript. Respiratory distress syndrome decreased from 10.5% (390/3700) at 34 weeks to 0.3% (140/41,764) at 38 weeks. Similarly, TTN decreased from 6.4% (n=236) to 0.4% (n=155), pneumonia from 1.5% (n=55) to 0.1% (n=62), and respiratory failure from 1.6% (n=61) Conclusions-In a contemporary cohort, late preterm birth, compared with term delivery, was associated with increased risk for respiratory distress syndrome and other respiratory morbidity. NIH Public Access

Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies.

BackgroundWiedemann–Steiner syndrome (WDSTS) is a rare genetic disorder characterized by facial gestalt, neurodevelopmental delay, skeletal anomalies and growth retardation, which is caused by variation of KMT2A gene. To date, only 2 Chinese WDSTS patients have been reported. Here, we report the phenotypes and KMT2A gene variations in 14 unrelated Chinese WDSTS patients and investigate the phenotypic differences between the Chinese and French cohorts. MethodsNext generation sequencing was performed for each patient, and the variants in the KMT2A gene were validated by Sanger sequencing. The phenotypes of 16 Chinese WDSTS patients were summarized and compared to 33 French patients.ResultsGenetic sequencing identified 13 deleterious de novo KMT2A variants in 14 patients, including 10 truncating, 2 missenses and 1 splicing variants. Of the 13 variants, 11 are novel and two have been reported previously. One of the patients is mosaic in the KMT2A gene. The variation spectra and phenotypic profiles of the Chinese WDSTS patients showed no difference with patients of other ethnicities; however, differ in the frequencies of several clinical features. We demonstrated that variations in the KMT2A gene can lead to both advanced and delayed bone age. We identified 6 novel phenotypes, which include microcephaly, deep palmar crease, external ear deformity, carpal epiphyseal growth retardation, dyslipidemia, and glossoptosis. In addition, patients harbored missense variants in the CXXC zinc finger domain of KMT2A showed more severe neurophenotypes.ConclusionOur study consists of the largest cohort of Chinese WDSTS patients that continues to expand the WDSTS phenotypic and variation spectrum. Our results support the notion that the CXXC zinc finger domain of KMT2A gene is a hotspot for missense variants associated with more severe neurophenotypes.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0909-0) contains supplementary material, which is available to authorized users.

Objective To determine the incremental yield of exome sequencing (ES) over chromosomal microarray analysis (CMA) or karyotyping in prenatally diagnosed non‐immune hydrops fetalis (NIHF). Methods A prospective cohort study (comprising an extended group of the Prenatal Assessment of Genomes and Exomes (PAGE) study) was performed which included 28 cases of prenatally diagnosed NIHF undergoing trio ES following negative CMA or karyotyping. These cases were combined with data from a systematic review of the literature. MEDLINE, EMBASE, CINAHL and http://ClinicalTrials.gov databases were searched electronically (January 2000 to October 2020) for studies reporting on the incremental yield of ES over CMA or karyotyping in fetuses with prenatally detected NIHF. Inclusion criteria for the systematic review were: (i) at least two cases of NIHF undergoing sequencing; (ii) testing initiated based on prenatal ultrasound‐based phenotype; and (iii) negative CMA or karyotyping result. The incremental diagnostic yield of ES was assessed in: (i) all cases of NIHF; (ii) isolated NIHF; (iii) NIHF associated with an additional fetal structural anomaly; and (iv) NIHF according to severity (i.e. two vs three or more cavities affected). Results In the extended PAGE study cohort, the additional diagnostic yield of ES over CMA or karyotyping was 25.0% (7/28) in all NIHF cases, 21.4% (3/14) in those with isolated NIHF and 28.6% (4/14) in those with non‐isolated NIHF. In the meta‐analysis, the pooled incremental yield based on 21 studies (306 cases) was 29% (95% CI, 24–34%; P < 0.00001; I2 = 0%) in all NIHF, 21% (95% CI, 13–30%; P < 0.00001; I2 = 0%) in isolated NIHF and 39% (95% CI, 30–49%; P < 0.00001; I2 = 1%) in NIHF associated with an additional fetal structural anomaly. In the latter group, congenital limb contractures were the most prevalent additional structural anomaly associated with a causative pathogenic variant, occurring in 17.3% (19/110) of cases. The incremental yield did not differ significantly according to hydrops severity. The most common genetic disorders identified were RASopathies, occurring in 30.3% (27/89) of cases with a causative pathogenic variant, most frequently due to a PTPN11 variant (44.4%; 12/27). The predominant inheritance pattern in causative pathogenic variants was autosomal dominant in monoallelic disease genes (57.3%; 51/89), with most being de novo (86.3%; 44/51). Conclusions Use of prenatal next‐generation sequencing in both isolated and non‐isolated NIHF should be considered in the development of clinical pathways. Given the wide range of potential syndromic diagnoses and heterogeneity in the prenatal phenotype of NIHF, exome or whole‐genome sequencing may prove to be a more appropriate testing approach than a targeted gene panel testing strategy. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

More than 2 cycles of RFA coagulation is the only independent risk factors of fetal death after RFA.

The chorionicity–based evaluation of the perinatal risk in twin pregnancies after assisted reproductive technology (ART) is lacking. A retrospective review was performed of all twin pregnancies monitored prenatally and delivered at our hospital between 2010 and 2014. Chorionicity was diagnosed by ultrasound examination at first trimester and confirmed by postnatal pathology. Pregnancy and perinatal outcomes were prospectively recorded. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated in a logistic regression model. A total of 1153 twin pregnancies were analyzed. The occurrence of preterm premature rupture of membranes (PPROM) was 3 times as frequent in monochorionic diamniotic (MCDA) twin pregnancies after ART as in those spontaneous counterparts (aOR 3.0; 95%CI 1.1–3.2). The prevalence of intrahepatic cholestasis of pregnancies (ICP) was significantly higher in dichorionic diamniotic (DCDA) twin pregnancies following ART compared to spontaneous DCDA pregnancies (aOR 3.3; 95%CI 1.3–5.6). Perinatal outcomes did not differ between two conception methods, either in MCDA or DCDA twin pregnancies. Based on differentiation of chorionicity, ART is associated with the increased risk of PPROM in MCDA twin pregnancies and with a higher rate of ICP in DCDA twin gestations. ART does not increase adversity of perinatal outcomes in twin pregnancies.