OBJECTIVE: To explore the genetic basis for a fetus with Cardiac-urogenital syndrome (CUGS). METHODS: A fetus with congenital heart disease identified at the Maternal Fetal Medical Center for Fetal Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University in January 2019 was selected as the study subject. Clinical data of the fetus was collected. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. RESULTS: Detailed fetal echocardiographic examination had revealed hypoplastic aortic arch. The results of trio-WES revealed that the fetus has harbored a de novo splice variant of the MYRF gene (c.1792-2A>C), for which both parents were of the wild-type. Sanger sequencing confirmed the variant to be de novo. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CNV-seq has identified no chromosomal anomalies. And the fetus was diagnosed with Cardiac-urogenital syndrome. CONCLUSION The de novo splice variant of the MYRF gene probably underlay the abnormal phenotype in the fetus. Above finding has enriched the spectrum of MYRF gene variants.
Female ; Humans ; DNA Copy Number Variations ; Fetal Diseases ; Fetus/abnormalities* ; Heart Defects, Congenital/genetics* ; Mutation ; Transcription Factors/genetics*

OBJECTIVE: To analyze the characteristics of antibody-specific distribution, laboratory detection results of hemolytic disease of the fetus and neonatal(HDFN) caused by irregular blood group antibodies other than ABO, and its correlation with the clinical situation. METHODS: The non-ABO-HDFN cases in our hospital from October 2012 to December 2021 were selected as the research objects, and the cases diagnosed with ABO-HDFN in the same period were randomly selected as the control group, and the data of antibody specific distribution, total bilirubin, direct antibodies, maternal history, age of the children, the presence or absence of combined ABO-HDFN, and whether to exchange/transfuse blood were retrospectively analyzed. The characteristics of non-ABO-HDFN in Jiangxi province were analyzed. RESULTS: The detection rate of non-ABO-HDFN in Jiangxi province increased. Among 187 non ABO-HDFN cases, the highest percentage of Rh-HDFN was detected (94.6%). Compared with the control group of ABO-HDFN, the non-ABO-HDFN had higher mean integral value of direct antibody, higher peak total bilirubin, and longer duration. Anti-M-HDFN may have severe disease but the direct antibody weak positive/negative, it was easy missed in clinical and delayed the treatment. There is no correlation between the specificity of irregular antibodies, the sex of the child, the mother's previous childbirth history, the presence or absence of combined ABO-HDFN and the need for blood exchange/transfusion(P>0.05). CONCLUSION The irregular antibodies of causing non ABO-HDFN in Jiangxi area are mainly Rh blood group system, followed by MNS blood group system. Understanding the characteristics of HDFN disease, serological features and the correlation with clinical indexes will help to detect and treat non ABO-HDFN in time and reduce the risk of complications.
Child ; Female ; Humans ; Infant, Newborn ; ABO Blood-Group System ; Blood Group Antigens ; Erythroblastosis, Fetal ; Fetus ; Hematologic Diseases/complications* ; Hemolysis ; Isoantibodies ; Retrospective Studies

Objective: To analysis the clinical characteristics of 400 fetuses with heart defects and the impactors of pregnancy decision making, and explore the influence of a multi-disciplinary team (MDT) cooperation approach on it. Methods: Clinical data of 400 fetuses with abnormal cardiac structure diagnosed at Peking University First Hospital from January 2012 to June 2021 were collected, which were divided into 4 groups according to the characteristics of fetal heart defects and the presence of extracardiac abnormalities or not: single cardiac defects without extracardiac abnormalities (122 cases), multiple cardiac defects without extracardiac abnormalities (100 cases), single cardiac defects with extracardiac abnormalities (115 cases), and multiple cardiac defects with extracardiac abnormalities (63 cases). The types of fetal cardiac structural abnormalities and genetic test results, and the detection rate of pathogenic genetic abnormalities, MDT consultation and management situation, and pregnancy decision of fetuses in each group were retrospectively analyzed. A logistics regression was used to analyze the influencing factors of fetal heart defects pregnancy decision. Results: (1) Among the 400 fetal heart defects, the four most common major types were ventricular septal defect 96 (24.0%, 96/400), tetralogy of Fallot 52 (13.0%, 52/400), coarctation of the aorta 34 (8.5%, 34/400), and atrioventricular septal defect 26 (6.5%, 26/400). (2) Among the 204 fetuses undergoing genetic examination, 44 (21.6%, 44/204) pathogenic genetic abnormalities were detected. (3) Detection rate of pathogenic genetic abnormalities (39.3%, 24/61) and pregnancy termination rate (86.1%, 99/115) in the single cardiac defects with extracardiac abnormalities group were significantly higher than those in the single cardiac defects without extracardiac abnormalities group [15.1% (8/53), 44.3% (54/122), respectively] and the multiple cardiac defects without extracardiac abnormalities group [6.1% (3/49), 70.0% (70/100), respectively, both P<0.05], and the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group and the multiple cardiac defects with extracardiac abnormalities group (82.5%,52/63) were significantly higher than that of the single cardiac abnormalities without extracardiac abnormalities group (both P<0.05). (4) After adjusting for age, gravity, parity and performed prenatal diagnosis, maternal age, the diagnosis of gestational age, prognosis grades, co-existence of extracardiac abnormalities, presence of pathogenic genetic abnormalities, and receiving MDT consultation and management were still independent influencing factors of termination of pregnancy of fetuses with cardiac defects (all P<0.05). A total of 29 (7.2%, 29/400) fetal cardiac defects received MDT consultation and management, and compared with those without MDT management, the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group [74.2%(66/89) vs 4/11] and the multiple cardiac defects with extracardiac abnormalities group [87.9%(51/58) vs 1/5] were lower, the differences were statistically significant respectively (all P<0.05). Conclusions: Maternal age, diagnosed gestational age, severity of cardiac defects, extracardiac abnormalities, pathogenic genetic abnormalities and MDT counseling and management are the influencing factors of fetal heart defects pregnancy decision. MDT cooperation approach influences pregnancy decision-making and should be recommended for the management of fetal cardiac defect to reduce unnecessary termination of pregnancy and improve pregnancy outcomes.
Pregnancy ; Female ; Humans ; Retrospective Studies ; Fetal Diseases/diagnosis* ; Heart Defects, Congenital/therapy* ; Fetus ; Decision Making ; Ultrasonography, Prenatal/methods*

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.
Female ; Humans ; Pregnancy ; Asian People ; Chromosome Aberrations ; Chromosome Deletion ; Chromosome Duplication/genetics* ; DNA Copy Number Variations/genetics* ; Fetal Diseases/genetics* ; Genetic Counseling ; Microarray Analysis ; Prenatal Care ; Prenatal Diagnosis ; Practice Guidelines as Topic

OBJECTIVE: To investigate the titer of IgG anti-A/B erythrocyte antibody in vivo of the neonate with hemolytic disease of newborn(HDN), and explore its clinical valua in evaluating the severity of HDN. METHODS: 300 neonates with HDN, 50 neonates with neonatal hyperbilirubinemiain and 50 healthy neonates were selected as research object and Microtubes Gel Test was used to detect the titer of IgG anti-A/B erythrocyte antibody in vivo. Their clinical data and their mothers' prenatal examination data were retrospectively analyzed. Three hemolysis tests (direct antiglobulin test, free antibody test and release test), irregular antibody screening, and the titer of IgG anti-A/B blood group antibody was determined by serological method. Red blood cells(RBC), hemoglobin(Hb), reticulocytes(Ret) and nucleated red cells were detected by hematology analyzer. Indirect bilirubin and albumin(Alb) were detected by biochemical analyzer. The relationship between the titer of IgG anti-A/B erythrocyte antibody in vivo and the severity of HDN was analyzed. RESULTS: There were six serological diagnosis modes in the HDN group,the difference between modes was statistically significant (P<0.05). The antibody titer relationship between HDN neonates and pregnant women was positive correlation(r=0.8302). The highest antibody titer of release test and free antibody test were 1∶32 and 1∶2, and the difference was statistically significant（P<0.05）. RBC, Hb and Alb in HDN patients were lower than those in neonatal hyperbilirubinemia patients and healthy neonates (P<0.05), and were negatively relevant with antibody titer in vivo (r=-0.8016). Bilirubin content in HDN patients were higher than those in neonatal hyperbiliru binemia patients and healthy neonates group(P<0.05), and was positively relevant with antibody titer in vivo (r=0.8731). The hospital day in HDN patients was significantly relevant with the antibody titer in vivo (r=0.8547), but not with the age, sex, weight and ABO blood types (P>0.05). CONCLUSION The detection of antibody titer in HDN patients can be used to evaluate the antibody concentration in vivo, predict the ability of antibody to induce erythrocyte hemolysis, and help to judge the serenrity and prognosis of HDN.
ABO Blood-Group System ; Bilirubin ; Blood Group Incompatibility ; Erythroblastosis, Fetal ; Erythrocytes ; Female ; Hematologic Diseases ; Hemolysis ; Humans ; Immunoglobulin G ; Infant, Newborn ; Pregnancy ; Retrospective Studies

OBJECTIVES: To establish a nomogram model for predicting the risk of death of very preterm infants during hospitalization. METHODS: A retrospective analysis was performed on the medical data of 1 714 very preterm infants who were admitted to the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University, from January 2015 to December 2019. These infants were randomly divided into a training cohort (1 179 infants) and a validation cohort (535 infants) at a ratio of 7∶3. The logistic regression analysis was used to screen out independent predictive factors and establish a nomogram model, and the feasibility of the nomogram model was assessed by the validation set. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, accuracy, and clinical applicability of the model. RESULTS: Among the 1 714 very preterm infants, 260 died and 1 454 survived during hospitalization. By the multivariate logistic regression analysis of the training set, 8 variables including gestational age <28 weeks, birth weight <1 000 g, severe asphyxia, severe intraventricular hemorrhage (IVH), grade III-IV respiratory distress syndrome (RDS), and sepsis, cesarean section, and use of prenatal glucocorticoids were selected and a nomogram model for predicting the risk of death during hospitalization was established. In the training cohort, the nomogram model had an AUC of 0.790 (95%CI: 0.751-0.828) in predicting the death of very preterm infants during hospitalization, while in the validation cohort, it had an AUC of 0.808 (95%CI: 0.754-0.861). The Hosmer-Lemeshow goodness-of-fit test showed a good fit (P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 10%-60% for the training cohort and 10%-70% for the validation cohort. CONCLUSIONS A nomogram model for predicting the risk of death during hospitalization has been established and validated in very preterm infants, which can help clinicians predict the probability of death during hospitalization in these infants.
Cesarean Section ; Female ; Fetal Growth Retardation ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; Nomograms ; Pregnancy ; Retrospective Studies

OBJECTIVES: To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC. METHODS: A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model. RESULTS: The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value. CONCLUSIONS Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.
Asphyxia/complications* ; Child ; Enterocolitis, Necrotizing/etiology* ; Female ; Fetal Growth Retardation ; Humans ; Hypoalbuminemia ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases/etiology* ; Nomograms ; Sepsis/complications*

OBJECTIVES: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome. RESULTS: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment. CONCLUSIONS ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.
Child ; Extracorporeal Membrane Oxygenation ; Humans ; Hypertension, Pulmonary/therapy* ; Infant, Newborn ; Lung Diseases ; Persistent Fetal Circulation Syndrome/therapy* ; Retrospective Studies ; Treatment Outcome

BACKGROUND: The fetal growth charts in widest use in China were published by Hadlock >35 years ago and were established on data from several hundred of American pregnant women. After that, >100 fetal growth charts were published around the world. We attempted to assess the impact of applying the long-standing Hadlock charts and other charts in a Chinese population and to compare their ability to predict newborn small for gestational age (SGA). METHODS: For this retrospective observational study, we reviewed all pregnant women ( n  = 106,455) who booked prenatal care with ultrasound measurements for fetal biometry at the Shenzhen Maternity and Child Healthcare Hospital between 2012 and 2019. A fractional polynomial regression model was applied to generate Shenzhen fetal growth chart ranges for head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL). The differences between Shenzhen charts and published charts were quantified by calculating the Z -score. The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating characteristic curves of published charts to predict neonatal SGA (birthweight <10th centile) were assessed. RESULTS: Following selection, 169,980 scans of fetal biometry contributed by 41,032 pregnancies with reliable gestational age were analyzed. When using Hadlock references (<3rd centile), the proportions of small heads and short femurs were as high as 8.9% and 6.6% in late gestation, respectively. The INTERGROWTH-21st standards matched those of our observed curves better than other charts, in particular for fat-free biometry (HC and FL). When using AC<10th centile, all of these references were poor at predicting neonatal SGA. CONCLUSIONS Applying long-standing Hadlock references could misclassify a large proportion of fetuses as SGA. INTERGROWTH-21st standard appears to be a safe option in China. For fat-based biometry, AC, a reference based on the Chinese population is needed. In addition, when applying published charts, particular care should be taken due to the discrepancy of measurement methods.
Infant, Newborn ; Child ; Female ; Pregnancy ; Humans ; Growth Charts ; Prenatal Care ; Ultrasonography, Prenatal/methods* ; Fetal Development ; Fetal Growth Retardation ; Gestational Age ; Fetus ; China ; Infant, Newborn, Diseases ; Observational Studies as Topic