A novel MED12 pathogenic variant in a female fetus with facial cleft and cardiac defects identified in the first trimester.

Trio exome sequencing was performed on a female fetus with an increased nuchal translucency, along with nasal bone hypoplasia, suspected cleft palate and abnormal outflow tract of the heart. A de novo heterozygous variant c.5500_5507del, p.(Tyr1834Argfs × 58) in the MED12 gene was detected. Loss-of-function variants in MED12 in females are associated with Hardikar syndrome (HS). A follow-up ultrasound at 15+5 weeks of gestation identified multiple fetal anomalies including bilateral cleft lip and palate, diaphragmatic hernia, atrioventricular septal defect, persistent truncus arteriosus, and bilateral renal pelvis dilation. Fetal autopsy confirmed the prenatal sonographic findings, and the MED12 variant was discussed by our multidisciplinary team to be the cause of fetal anomalies. Our case is the first prenatal one in which HS was diagnosed due to first trimester structural malformations. This case report presents another example of early identification of a major anomaly which allows earlier genetic diagnosis and more time for clinical management.

Fetal Rhabdomyoma Leads to Family Diagnosis of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder characterized by the growth of numerous noncancerous tumors in many parts of the body. It is highly variable in clinical presentations, including a wide range of cognitive, behavioral, and psychiatric manifestations. Of all the possible manifestations, cognitive and behavioral problems are the greatest concern to parents and physicians. In this study, two fetuses were identified to have rhabdomyomas by prenatal ultrasound. Carefully inquired familial medical history revealed other symptoms of TSC such as skin lesions or psychiatric problems in family members in the two families. Both fetuses and family members with positive clinical symptoms were confirmed to carry a familial TSC2 variant. Our study indicates that fetal echocardiography is not just the evaluation of the fetal heart. When fetal cardiac rhabdomyomas are diagnosed, a full family medical history and clinical assessment for TSC in family members should be undertaken.

Megacystis in the First Trimester as an Unreported Sonographic Finding of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Confirmed by Whole-exome Sequencing.

A pregnant woman was revealed to have fetal univentricular heart and megacystis by a routine first-trimester ultrasound. Chorionic villus sampling with the use of karyotyping and microarray found no causative etiologies. A further investigation with whole-exome sequencing (WES) demonstrated a FOXF1 variant. Autopsy confirmed the prenatal findings, and a histological study of the lungs showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This study indicates that although ultrasound itself has no ability of the identification of pulmonary histological malformations associated with ACDMPV, the early markers of univentricular heart and megacystis might alert clinicians to consider this genetic disorder which is facilitated considerably by the increasingly used WES in prenatal diagnosis.

Adducted Thumb in the First Trimester of Pregnancy: An Early Clue to Prenatal Diagnosis of L1 Syndrome.

A pregnant woman was revealed to have an unusual position of the fetal hand by a routine 12-week ultrasound. Bilateral adducted thumbs and a male phenotype were confirmed by another ultrasound at 14 weeks' gestation. A structural survey at 18 weeks revealed fetal hydrocephalus with severe bilateral ventriculomegaly. The pregnancy was terminated, and postnatal examination with trio exome sequencing detected a hemizygous deletion (1,511 bp in size) variant of L1CAM gene in the fetus, inherited from the mother. The fetus was diagnosed as L1 syndrome (X-linked hydrocephalus). A family study found that this was a familial mutant allele. This study demonstrates that fetal hand abnormalities can be identified in the first trimester. Adducted thumbs might indicate the maldevelopment of the fetal brain, and therefore, examination of fetal hands and fingers should be integrated into fetal anomaly scans.

Rapid prenatal diagnosis of skeletal dysplasia using medical trio exome sequencing: Benefit for prenatal counseling and pregnancy management.

OBJECTIVE: The aim of this study is to explore the utility of rapid medical trio exome sequencing (ES) for prenatal diagnosis using the skeletal dysplasia as an exemplar. METHOD: Pregnant women who were referred for genetic testing because of ultrasound detection of fetal abnormalities suggestive of a skeletal dysplasia were identified prospectively. Fetal samples (amniocytes or cord blood), along with parental blood, were send for rapid copy number variations testing and medical trio ES in parallel. RESULTS: Definitive molecular diagnosis was made in 24/27 (88.9%) cases. Chromosomal abnormality (partial trisomy 18) was detected in one case. Sequencing results had explained the prenatal phenotype enabling definitive diagnoses to be made in 23 cases. There were 16 de novo dominant pathogenic variants, four dominant pathogenic variants inherited maternally or paternally, two recessive conditions with pathogenic variants inherited from unaffected parents, and one X-linked condition. The turnaround time from receipt of samples in the laboratory to reporting sequencing results was within 2 weeks. CONCLUSION: Medical trio ES can yield very timely and high diagnostic rates in fetuses presenting with suspected skeletal dysplasia. These definite diagnoses aided parental counseling and decision making in most of cases.

Development and validation of an artificial intelligence assisted prenatal ultrasonography screening system for trainees.

OBJECTIVE: Fetal anomaly screening via ultrasonography, which involves capturing and interpreting standard views, is highly challenging for inexperienced operators. We aimed to develop and validate a prenatal-screening artificial intelligence system (PSAIS) for real-time evaluation of the quality of anatomical images, indicating existing and missing structures. METHODS: Still ultrasonographic images obtained from fetuses of 18-32 weeks of gestation between 2017 and 2018 were used to develop PSAIS based on YOLOv3 with global (anatomic site) and local (structures) feature extraction that could evaluate the image quality and indicate existing and missing structures in the fetal anatomical images. The performance of the PSAIS in recognizing 19 standard views was evaluated using retrospective real-world fetal scan video validation datasets from four hospitals. We stratified sampled frames (standard, similar-to-standard, and background views at approximately 1:1:1) for experts to blindly verify the results. RESULTS: The PSAIS was trained using 134 696 images and validated using 836 videos with 12 697 images. For internal and external validations, the multiclass macro-average areas under the receiver operating characteristic curve were 0.943 (95% confidence interval [CI], 0.815-1.000) and 0.958 (0.864-1.000); the micro-average areas were 0.974 (0.970-0.979) and 0.973 (0.965-0.981), respectively. For similar-to-standard views, the PSAIS accurately labeled 90.9% (90.0%-91.4%) with key structures and indicated missing structures. CONCLUSIONS: An artificial intelligence system developed to assist trainees in fetal anomaly screening demonstrated high agreement with experts in standard view identification.

Carbon Nanofiber Membranes Loaded with MXene@g-C3N4: Preparation and Photocatalytic Property.

In this study, a Ti3C2 MXene@g-C3N4 composite powder (TM-CN) was prepared by the ultrasonic self-assembly method and then loaded onto a carbon nanofiber membrane by the self-assembly properties of MXene for the treatment of organic pollutants in wastewater. The characterization of the TM-CN and the C-TM-CN was conducted via X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectrometer (FTIR) to ascertain the successful modification. The organic dye degradation experiments demonstrated that introducing an appropriate amount of Ti3C2 MXene resulted in the complete degradation of RhB within 60 min, three times the photocatalytic efficiency of a pure g-C3N4. The C-TM-CN exhibited the stable and outstanding photocatalytic degradation of the RhB solution over a wide range of pH values, indicating the characteristics of the photodegradation of organic pollutants in a wide range of aqueous environments. Furthermore, the results of the cyclic degradation experiments demonstrated that the C-TM-CN composite film maintained a degradation efficiency of over 85% after five cycles, thereby confirming a notable improvement in its cyclic stability. Consequently, the C-TM-CN composite film exhibits excellent photocatalytic performance and is readily recyclable, making it an auspicious eco-friendly material in water environment remediation.

[Study on mode of delivery and singleton newborns term birth weight in 3 hospitals].

OBJECTIVE: To study newborns weight in singleton term births and the association between newborns birth weight and mode of delivery in 3 hospitals. METHODS: From Jan. 2005 to Dec. 2009, 13 963 singleton term live neonates born in the Department of Obstetrics and Gynecology of Peking University First Hospital (PU group), 6519 neonates in Affiliated Hospital of Binzhou Medical College (BMC group,) and 8725 neonates in Miyun Hospital Affiliated to Capital Medical University, Yanjing Medical College (MYC group) were enrolled in this retrospective study. The newborns weight and the rate of macrosomia was calculated and compared. Those newborns from PU group and MYC group were divided into 2288 neonates at macrosomia group and 20 400 neonates at non-macrosomia group, their mode of deliveries were analyzed. RESULTS: (1) The mean neonatal birth weight were (3386 ± 414) g at PU group, (3389 ± 446) g at BMC group and (3445 ± 449) g at MYC group. Neonates born weight in MYC was significantly higher than those from in PU group and BMC group (P = 0.000). Neonates born weight in BMC showed higher than those in PU group, which did not reached statistical difference (P = 0.638). (2) The incidence of macrosomia were 7.935% (1108/13 963) in PU group, 9.802% (639/6519) in BMU group and 13.524% (1180/8725) in MYU group. The incidence of macrosomia in MYC group was higher than those in PU and BMC group, the incidence of macrosomia in BMC group was higher than that in PU group, which reached statistically difference (P = 0.000). (3)The proportion of cesarean delivery were 75.306% (1723/2288) at macrosomia group, 50.765% (10 356/20 400) at non-macrosomia group, which showed statistical difference (P = 0.000). CONCLUSIONS: (1) The difference of newborns birth weight existed in different administrative level hospital. (2) The risk of cesarean delivery due to macrosomia is higher than that of non-macrosomia. (3) Obstetricians should pay more attention to nutrition in gestation period to lessen the incidence of macrosomia and cesarean section.

[Investigation into the clinical suitability of Institute of Medicine 2009 guidelines regarding weight gain during pregnancy for women with full term singleton fetus in China].

OBJECTIVE: To study whether the current Institute of Medicine (IOM) pregnancy weight gain recommendations vary by pre-pregnancy body mass index (BMI) was suitable to Chinese people. METHODS: A study was conducted on 4736 term singleton live birth gravidas, who were diagnosed normal glucose metabolism and delivered in Peking University First Hospital in 2005 and 2009, by reviewing the medical records. Based on the pre-pregnant BMI, the selected cases were divided into 3 groups: low body mass group (BMI < 18.5 kg/m(2), n = 465), normal body mass group (BMI 18.5 - 24.9 kg/m(2), n = 3549), over body mass group (BMI ≥ 25 kg/m(2), n = 722). All the cases were divided into 3 subgroups based on pregnancy weight gain as below, within, and above the IOM recommendations in each pre-pregnant BMI group. Totally 4736 newborns were divided by birth weight into 3 groups: normal birth weight group (weight 2500 - 4000 g, n = 4339), macrosomia group (weight ≥ 4000 g, n = 359) and low birth weight group (weight < 2500 g, n = 38). The difference of age, gestational age, pre-pregnant weight, pre-pregnant BMI and history of delivery of cases between 2005 and 2009 were analyzed. The difference of pregnancy outcome of women whose gestational weight gain was below, within, and above the IOM recommendations was analyzed. RESULTS: (1) Compared to mothers with pregnancy weight gain within IOM recommendations in low body mass group, risk of low birth weight in offspring was elevated tendency with pregnancy weight gain below IOM recommendations (OR = 3.71, 95%CI: 0.97 - 14.12, P = 0.055). (2) In normal body mass group, compared to women with pregnancy weight gain within IOM recommendations, risk of macrosomia in offspring was elevated with pregnancy weight gain above IOM recommendations (OR = 2.14, 95%CI: 1.62 - 2.83, P < 0.01). (3) In over body mass group, compared to women with pregnancy weight gain within IOM recommendations, risk of macrosomia in offspring was elevated (OR = 3.25, 95%CI: 1.65 - 6.39, P = 0.001) and risk of hypertensive disorders complicating pregnancy was high (OR = 1.79, 95%CI: 1.04 - 3.09, P = 0.037) in women with pregnancy weight gain above IOM recommendations. CONCLUSION: The current IOM pregnancy weight gain recommendations vary by pre-pregnancy BMI may be suitable to Chinese people.

Intrafamilial Phenotypic Heterogeneity in a Chinese Family with a POLR1D p.Q31Rfs*10 Variant: A Challenge in Prenatal Diagnosis.

Introduction: Treacher Collins syndrome (TCS), also known as mandibulofacial dysostosis, is an inherited craniofacial defect. Here, we report a TCS family in which the members carry the same POLR1D variant but present with phenotypic variability. Case Presentation: A 19-year-old healthy primigravida was revealed by ultrasound at 12 weeks of gestation to have a fetus with micrognathia. Prenatal genetic testing detected a heterozygous single-nucleotide deletion (NM_015972:c.91del, p.Q31Rfs*10) in the POLR1D gene, inherited from the healthy mother. Variants of POLR1D have been reported to be associated with TCS. Family studies found that a paternal healthy cousin of the mother had a similar pregnancy outcome, with a fetus of TCS and the same POLR1D variant. Discussion: Our study results pose a great challenge to prenatal diagnosis of TCS. The prenatal diagnosis cannot only rely on genetic testing. Instead, an early detailed sonographic survey will be helpful for the identification of TCS.