Objective:To investigate the clinical and molecular genetic features of neonatal congenital Netherton syndrome (NS) caused by mutations in serine protease inhibitor of Kazal type 5 ( SPINK5) gene. Methods:This study retrospectively analyzed the clinical data of an NS neonate admitted to Shanghai Children's Hospital in November 2018. SPINK5 gene was analyzed using high-throughput sequencing and Sanger sequencing. Relevant articles were retrieved from various databases including China National Knowledge Infrastructure, Wanfang and PubMed, and the reported cases who were diagnosed as NS within two months after birth with SPINK5 gene sequencing results were reviewed. Clinical features, gene mutations, treatment and follow-up results of NS were summarized using descriptive statistical analysis. Results:The patient presented with diffuse erythema and desquamation, sparse hair and repeated infections shortly after birth. Laboratory tests revealed elevated IgE (111 IU/ml) and "invagination-like" change in the hair under optical microscope. SPINK5 gene analysis found that there were compound heterozygous mutations of c.2468dup (p.Lys824Glufs*4) and c.377_378del (p.Tys126*) in the child. The pedigree analysis found that the two mutations were respectively inherited from the father and the mother, which supported the diagnosis of NS caused by SPINK5 gene mutation. Though skin rash improved after comprehensive treatments including anti-infection therapy, gamma globulin injection and skincare, the patient suffered from recurrent infection and was discharged from the hospital after giving up treatment and died of infection at two months old. Eleven NS cases were retrieved from literature and altogether 12 cases were analyzed here. The most common clinical manifestations in the 12 patients were early skin diffuse erythema and desquamation (12/12), infection (8/12), dry hair (7/12), hypernatremia dehydration (7/12), high IgE (5/12), growth retardation (4/12), respiratory failure (3/12), atopic constitution (2/12), diarrhea (2/12), dysphagia (1/12), hypothermia (1/12), wheezing (1/12), hypertension (1/12), liver failure (1/12) and metabolic alkalosis (1/12). Conclusions:NS is caused by SPINK5 gene mutation with atypical manifestations in neonates. Neonates with diffuse erythema and desquamation of the skin, repeated infections, dry hair and especially with high blood IgE should be considered the possibility of NS. Genetic testing is conducive to early diagnosis, guiding treatment decisions and providing a basis for genetic counseling.

Objective:To investigate the neonatal outcomes and prognosis of fetuses who were prenatally diagnosed with intraventricular hemorrhage(IVH) to provide evidence for clinical consultation and management.Methods:Clinical data of fetal IVH cases ( n=89) diagnosed by fetal neurosonogram (NSG) in Peking University First Hospital from January 2012 to April 2020 were retrospectively collected, and neonatal outcomes were analyzed, involving fetuses with different grades of IVH and coexisting abnormalities. These patients were followed up for more than three months after birth. Two child development screening systems, Ages & Stages Questionnaires (Third Edition) (ASQ-3) and Ages & Stages Questionnaires: Social-Emotional (ASQ-SE), were used to assess the development of the patients from several aspects including physical growth, oral communication, motor ability and social emotions. Descriptive statistical analysis was used in this study. Results:(1) A total of 89 fetuses were enrolled and 66.3% (59/89) of them underwent fetal cranial MRI examination after ultrasound diagnosis. Among these 59 cases, 32(54.2%) had the same results with fetal NSG; 20(33.9%) with the diagnosis of remote ventricular cystic hemorrhage by fetal NSG, but misdiagnosed by MRI, were all confirmed by neonatal craniocerebral ultrasound; 7(11.9%) were lost to follow-up or terminated. In addition to IVH that was consistent with the ultrasound diagnosis, MRI also found three cases of cortical malformation, three cases of subdural hemorrhage and two cases of cerebral parenchymal hemorrhage. (2) Among the 89 cases, 37 (41.6%) underwent neonatal craniocerebral ultrasound examination after birth showing small amount of remote IVH, which was consistent with previous fetal NSG diagnosis. (3) There were 38 cases complicated by lateral ventricular widening (three lost to follow-up, 18 were terminated , one died in uterus, 15 with good and one with poor outcome), 10 cases by severe IVH sequelae (one lost to follow-up and nine were terminated) and 10 by craniocerebral malformation (one lost to follow-up, eight were terminated and one with poor neonatal prognosis). Two cases with extracranial malformation (ureteropelvic junction obstruction) were healthy after birth. (4) There were 29, 30, 16 and 14 cases of gradeⅠ,Ⅱ,Ⅲ andⅣ of fetal IVH, respectively. Among all cases, 12 were lost to follow-up; three died in uterus (all with gradeⅣ IVH); 31 were terminated and 43 were born and followed up. During the follow-up of the 43 cases, two (one grade Ⅰ case with corpus callosum dysplasia and one grade Ⅲ case with fetal cytomegalovirus infection) had poor prognosis, while the other 41 (one gradeⅢ, 17 gradeⅡ and 23 gradeⅠcases) showed no severe abnormalities.Conclusions:Fetal NSG is the first choice in screening fetal IVH and MRI can be a valuable aid. The neonatal prognosis may be associated with the grade of hemorrhage and coexisting abnormalities. Fetuses with isolated grade Ⅰ or Ⅱ IVH usually have a relatively good prognosis.

Objective:To explore the genetic background in monochorionic diamniotic (MCDA) twins discordant for karyotypes.Methods:This study retrospectively analyzed four pregnant women who were diagnosed as having MCDA twins with prenatal diagnostic indications by ultrasound at Maternity and Child Health Care of Guangxi Zhuang Autonomous Region from January 2016 to December 2019. Dual amniocentesis was performed for all cases guided by ultrasound and the twin amniotic fluids were taken for karyotyping and single nucleotide polymorphism (SNP) array testing. Zygosity was determined by SNP genotype analysis.Results:The karyotypes of four MCDA twins were 47,XX,+18 and 46,XX, 45,X and 46,XX, 47,XXY[17]/46,XY[33] and 47,XXY, and 47,XX,+21 and 46,XX, respectively. The results of SNP were arr(18)×3 and arr(1-22,X)×2, arr(X)×1 and arr(1-22,X)×2, arr(X)×1~2,(Y)×1 and arr(X)×2,(Y)×1, arr(21)×3 and arr(21)×2~3. All of them were monozygotic twins according to the SNP genotypes. Three out of the four cases chose to terminate the pregnancy due to fetal chromosomal abnormalities and one was lost to follow-up. One gave birth to a healthy child in the next pregnancy.Conclusions:Clinicians should be alert to the discordant karyotypes in MCDA twins, of which the mechanism is yet to be explored.

Objective:To analyze the genetic test results and ultrasonographic markers of 41 fetuses with short femurs and their relationship.Methods:This study retrospectively analyzed 41 fetuses who were diagnosed with short femurs by ultrasound during 19-37 gestational weeks and underwent prenatal genetic examination at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2019. According to the results of genetic examination, these cases were divided into three groups after excluding three cases of variants of unknown significance: genetically normal group, chromosome variation (including chromosomal aneuploidy and pathogenic or likely pathogenic copy number variations) group, and gene mutation (including pathogenic or likely pathogenic gene mutations) group. According to the head circumference (HC), abdominal circumference (AC) and femur length (FL), Z FL, FL/HC, FL/AC, ΔZ H-F and ΔZ H+A-2F for each fetus were calculated. One-way ANOVA and LSD- t test were used for statistical analysis. Results:(1) Among the 41 fetuses with short femurs, there were 28 in the genetically normal group, five in the chromosome variation group, three with chromosome variations of unknown significance and five in the gene mutation group. (2) In the genetically normal, chromosome variation and gene mutation groups, Z FL values were -2.78±0.77, -4.36±0.69 and -4.69±0.70; FL/HC ratios were 0.178±0.011, 0.170±0.010 and 0.131±0.022; FL/AC ratios were 0.197±0.013, 0.186±0.011 and 0.151±0.017; ΔZ H-F values were 2.49±1.09, 3.53±1.28 and 8.17±1.30; ΔZ H+A-2F values were 4.44±2.00, 6.78±2.20 and 14.28±1.26, respectively. The differences in Z FL values between the genetically normal group and the chromosome variation group as well as the gene mutation group were statistically significant (both P<0.05); so were the differences in FL/HC, FL/AC and ΔZ H-F values between the gene mutation group and the genetically normal group as well as the chromosome variation group (all P<0.05) and in any pairwise comparison of ΔZ H+A-2F among the three groups (all P<0.05). Conclusions:The genetic etiology of fetal short femurs is mainly related to chromosomal variations (including chromosomal aneuploidy and pathogenic or likely pathogenic copy number variations) and gene mutation. In fetuses with chromosome variation and gene mutation, the degree of the femoral development delay relative to the development of HC and AC is worse than that in the normal genetic results group.

Objective:To investigate the clinical characteristics of neonatal congenital tongue base cyst.Methods:This retrospective study involved 35 neonates with congenital tongue base cyst diagnosed in the neonatal intensive care unit (NICU) of Xi'an Children's Hospital from June 2013 to December 2019. General information, clinical manifestations, supplementary results, treatment and prognosis of these babies were described.Results:(1) The median age at the onset of the disease was 12.5 (0~28) d and the median age at admission was 15 (0~28) d for these babies. The main clinical manifestations were laryngeal stridor (28/35, 80.0%), inspiratory dyspnea and crying, especially when feeding (26/35, 74.3%) and choking and spitting with feeding (23/35, 65.7%). (2) Among the 35 cases, 15 (42.9%) required emergency endotracheal intubation due to significant dyspnea when were admitted to the NICU and five out of them were considered for having tongue base mass under laryngoscopy, while the other 10 cases underwent bedside electronic laryngoscopy after endotracheal intubation, in which space-occupying lesions were found. Tongue base cyst was considered in seven cases with laryngeal stridor complicated by protracted pneumonia using fiberoptic bronchoscopy. The other 13 cases were examined by electronic laryngoscope and considered as tongue base cyst. Thirty-five cases underwent cervical ultrasound and only five of them were considered as tongue base tumor. Thirty-two cases underwent cervical CT scan and only two of them were normal. Three cases were found to have tongue base cyst by cranial MRI. (3) Thirty-four cases were treated by radiofrequency ablation assisted with self-retaining microlaryngoscope and general anesthesia, while the other one firstly received puncture and drainage under direct laryngoscope due to the difficult intubation because of the huge tongue base cyst and then underwent surgery when stable. Only one case (2.9%) relapsed after surgical treatment during regular follow-up.Conclusions:Neonatal congenital tongue base cyst has an early onset and atypical clinical manifestations. Electronic laryngoscopy/fiberoptic bronchoscopy combined with neck CT or MRI examination should be performed promptly in patients with laryngeal stridor and inspiratory dyspnea to facilitate the accurate diagnosis and timely surgery is required for.

Objective:To explore the predictive value of a scoring model based on MRI images for diagnosing invasive placenta accreta and associated adverse clinical outcomes.Methods:This retrospective cohort study involved 260 patients delivered at Peking University Third Hospital from January 2015 to December 2018, who were suspected to be placenta accreta with two or more ultrasound image findings and underwent MRI examination. Placenta accreta was finally diagnosed and classified based on the intraoperative clinical findings or pathological examination. Adverse clinical outcomes were defined as intraoperative bleeding ≥1 500 ml and/or having hysterectomy. Quantitative and qualitative interpretation of five MRI signs were performed, including intraplacental low-intensity band on T2 weighted imaging, abnormal intraplacental vascularization, vascularization of uterovesical interface, uterine bulging and cervical involvement. Chi-square and t test were used for univariate analysis of the five MRI signs and the receiver operating characteristics (ROC) curve of each MRI sign for predicting invasive placenta accreta and adverse clinical outcomes were drawn. The predictive value was assigned as 1 when ≥ the cutoffs that matched to the maximum Yoden index values, and was assigned as 0 when below the cutoffs. A scoring model based on the five MRI signs was established, ROC curves of the model for predicting invasive placenta accreta and adverse clinical outcomes were drawn and the area under the curve (AUC), sensitivity, specificity and Youden index were calculated. Results:(1) Univariate analysis showed that all five MRI signs were significantly associated with invasive placenta accreta and adverse clinical outcomes. Except for cervical involvement, the other four signs had an AUC value of greater than 0.5 in predicting invasive placenta accreta and adverse clinical outcomes. (2) The predictive cut-off values of abnormal intraplacental vascularization image and intraplacental dark band area on T2 weighted imaging were 2.0 cm 2 and 0.6 cm 2, respectively, and were all 1.0 for the other three signs. The AUC value of MRI signs-based scoring model for predicting invasive placenta accreta was 0.863. When the score was ≥ 2 points, the diagnostic sensitivity was 0.836 and the specificity was 0.726. The scoring model predicted adverse clinical outcomes with an AUC of 0.841. When the score was ≥3 points, the predictive sensitivity was 0.707 and the specificity was 0.818. Conclusions:The scoring model based on MRI signs is of good value for the diagnosis of invasive placenta accreta and the prediction of adverse clinical outcomes.

We report the prenatal diagnosis and treatment of a case of primary right pulmonary deficiency. A routine ultrasound examination at 23 +6 weeks of gestation found an absent right lung, enlarged left lung, and dextroposition of the heart in a female fetus. Karyotype and chromosome microarray analysis of the amniotic fluid was normal. After multidisciplinary consultation, the pregnant woman chose to continue the pregnancy and had a normal delivery at 39 +2 gestational weeks. Apgar scores were ten at both 1 min and 5 min after birth, with no abnormal appearance of the baby, or signs of thoracic collapse other than no obvious respiratory sounds in the right lung. Both postnatal chest X-ray and CT scan indicated an undeveloped right lung. Cardiac ultrasonography revealed the absence of the right pulmonary artery and vein. The patient's breathing was stable during hospitalization and she was discharged eight days after birth. The infant was followed up at five months, and the growth and development were comparable to children of the same age.

Fetal alloimmune thrombocytopenia (FAIT) is a severe perinatal complication, which can seriously affect fetal development, and may even lead to intrauterine hemorrhage and intrauterine death. There are controversies in the clinical diagnosis and treatment of the disease due to its low incidence and limited treatment experience. This paper reviews the progress to date in understanding the condition, incidence, screening of high-risk factors, prenatal and delivery management of FAIT based on domestic and foreign guidelines, in order to help obstetricians in the clinical management of FAIT.

Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.

Objective:To summarize and compare the characteristics of oral microbiota in women during the preconception period and the third trimester.Methods:This retrospective cohort study involved 55 women who were recruited in the Preconceptional Offspring Trajectory Study (PLOTS) conducted by Fudan University and followed up to the third trimester in the Maternal and Child Health Care Hospital of Jiading District of Shanghai from September 2016 to December 2019. A total of 110 unstimulated saliva samples were collected in the preconception period ( n=55) and the third trimester ( n=55). Features of oral microbiota in the samples were analyzed by 16S rRNA gene-based sequencing. Moreover, the related factors were also analyzed. Paired t test or Wilcoxon matched-pairs signed-ranks test were used to analyze the differences in α-diversity during preconception and the third trimester; t test, analysis of variance (ANOVA), Kruskal-Wallis test and Mann-Whitney U test for comparison between groups with different characteristics and permutational multivariate analysis of variance (PerMANOVA) for β-diversity were used; Linear discriminant analysis (LDA) effect size (LEfSe 1.0) was used to identify the iconic oral flora. Results:(1) The Ace index of oral microbiota was significantly lower in the third trimester than that in the preconception period [661.14(578.15-752.85) vs 730.64 (632.40-911.00), T=1 077.00, P=0.010]. There was also a significance difference in β-diversity ( F=12.539, R2=0.104, P=0.001). Some species such as Saccharibacteria_TM7_G3, Prevotella_7, Absconditabacteria_SR1_G1, Porphyromonas, Ruminococcaceae_UCG_014, Prevotella, Peptostreptococcus, Prevotella_2, Alloprevotella, Parvimonas, Solobacterium and Eubacterium_nodatum_group in saliva were statistically more abundant in the third trimester than those in the preconception period (all P<0.05). (2) The third-trimester Shannon index was lower among those with lower income [5.44 (5.08-5.77) vs 5.75 (5.44-6.12), U=219.00, P=0.029] and those with gargle habit after meal or dessert [5.36 (4.91-5.48) vs 5.72 (5.44-6.05), U=374.00, P=0.046]. Conclusions:The features of oral microbiota vary in women during the preconception period and the third trimester. There is a significant increase in the abundance of oral pathogenic and opportunistic bacteria in the third trimester.