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.