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 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 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 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*

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

International guidelines regarding the role of intravenous immunoglobulin (IVIG) in the management of Rh- and ABO-mediated haemolytic disease of the newborn was drafted by an international panel of experts in the fields of hematology, neonatology, and blood transfusion and was published in British Journal of Haematology on March 16, 2022. The guidelines summarize the evidence-based practice of IVIG in Rh- and ABO-mediated haemolytic disease of the newborn and propose related recommendations. The guidelines recommend that IVIG should not be applied as a routine treatment regimen for Rh- and ABO-mediated haemolytic disease of the newborn in order to reduce exchange transfusion (ET), and the best time to apply IVIG remains unclear in the situations where hyperbilirubinaemia is severe (approaching or exceeding the ET threshold) or ET cannot be implemented. These guidelines are formulated with rigorous methods, but with the lower quality of evidence.
Infant, Newborn ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Erythroblastosis, Fetal/drug therapy* ; Exchange Transfusion, Whole Blood ; Hematologic Diseases ; Hyperbilirubinemia

Objective: To analyze the physical growth of preterm infants with different intrauterine growth patterns. Methods: A total of 10 856 preterm infants who were born in various districts of Haikou City from October 1st, 2015 to June 1st, 2021 and received regular health care and management were retrospectively enrolled. The preterm infants were divided into appropriate for gestational age (AGA), small for gestational age (SGA) and large for gestational age (LGA) groups according to different intrauterine growth patterns. The general characteristics of preterm infants in different groups were compared by H test (Kruskal and Wallis) or Chi-squared test. And the developmental curves were plotted by local regression (LOESS) with their physical growth indexes. Results: Of the 10 856 preterm infants, 6 317 were boys and 4 539 were girls. The gestational age at birth was 35 (34, 36) weeks, and the birth weight was 2.5 (2.1, 2.8) kg. There were 754 (6.9%) SGA, 9 301 (85.7%) AGA, and 801 (7.4%) LGA preterm infants. All preterm infants were followed up until 18 months of corrected age. The birth weight of the SGA group was lower than that of the AGA and LGA groups (Z=2 274.93, P<0.001). The proportion of exclusive breastfeeding at the first health care interview was higher in the AGA group (68.6% (6 378/9 301)) than in the SGA group (62.9% (474/754)) (χ²=13.82, P=0.003). The LOESS curving fitting showed that the weight and height of the preterm infants in all the 3 groups increased rapidly during 0-6 months of corrected age. The regression prediction values of weight for age Z-score (WAZ), height for age Z-score (HAZ) and weight for height Z-score (WHZ) were around 0 s, while the regression prediction values of these three indicators in SGA were all below 0 s but greater than -1 s. The rates of low birth weight, growth retardation and wasting during 0-17 months of corrected age were 0.3% (16/4 838)-1.9% (47/2 506), 0.4% (18/4 838) -2.4% (51/2 124), and 2.1% (88/4 135) -4.4% (214/4 838) in AGA groups, and 0 (0/296) -1.0% (2/199), 0 (0/341) -1.6% (3/186) and 1.0% (2/199) -2.6% (9/341) in LGA group, whereas 7.6% (25/330) -16.8% (28/167), 5.2% (17/330)-10.6%(32/303) and 3.9% (3/77) -12.6% (21/167) in SGA group. In addition, the monthly growth of weight and height of preterm infants in all the 3 groups decreased with the increasing age, and the monthly weight gain. The length increment was 4.0 cm/month during corrected 0-2 month of age and 2.4 cm/month during corrected 2-5 month of age in the SGA preterm infants. Conclusions: Most of the preterm infants could have an appropriate catch-up growth, but the growth and development in the SGA preterm infants lags behind that of their AGA and LGA peers. The physical growth of SGA premature infants should be paid more attention to, to timely correct the growth deviations.
Birth Weight ; Child, Preschool ; Female ; Fetal Growth Retardation ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Small for Gestational Age ; Male ; Retrospective Studies

Objective: To investigate the occurrence of live-born twins with birth weight-discordance and its relationship to adverse birth outcomes. Methods: A retrospective analysis was performed on 4 011 pairs of live-born twins in the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020. Based on the birth-weight discordance (∆BW, ∆BW=(birth-weight_big-birth-weight_small)/birth-weight_big×100%)), twins were divided into 4 groups, including ∆BW≤15%,>15%-20%,>20%-25%, and>25%. The differences in maternal and neonatal outcomes among 4 groups were explored. Then the correlation between ∆BW and neonatal adverse outcomes were explored. Results: The ΔBW was 9 (4, 16)% and males were accounted for 53.8% (4 315 cases) of 4 011 pairs of twins. The gestational age was (35.3±2.7) weeks at birth. There were 2 908 pairs (72.5%) of twins with ΔBW≤15%, 481 pairs (12.0%) with ΔBW>15%-20%, 281 pairs (7.0%) with ΔBW 20%-≤25%, and 341 twin pairs (8.5%) with ΔBW>25%. With ∆BW of 20% as the diagnostic cutoff, the incidence of birth weight discordance was 15.5% (622/4 011). The proportion of natural births in the ∆BW≤15% group was higher than that in the ∆BW>15%-20% group (10.5% (288/2 740) vs. 6.3% (29/463), P<0.008 3). The ∆BW>25% group had a significantly higher prevalence of maternal hypertensive disorders during pregnancy than that of the other 3 groups (25.5% (87/341) vs. 16.7% (47/281) vs.17.3% (83/480) vs. 13.8% (400/2 899), all P<0.008 3). Univariate analysis found that the ΔBW>25% group had a lower gestational age and a higher rate of preterm birth than the other groups. The rate of extremely low birth weight (ELBW) or very low birth weight (VLBW), small for gestational age (SGA), and transferring to the department of neonatology in the smaller twins were significantly different among the 4 groups (all P<0.05). Multivariate analysis showed that higher degree of birth weight discordance was all positively associated with the rate of ELBW, SGA, and transferring to the department of neonatology in smaller twin, even after adjusting maternal age and gestational hypertension, year of birth, mode of delivery, gender, and gestational age (all P<0.05). Moreover, the Mantel-Haenszel test also indicated that there were significantly low to moderate correlations between ΔBW and the unfavorable outcomes (r=0.22, 0.53, 0.21, all P<0.001, respectively). The receiver operating characteristic (ROC) curve found that adverse birth outcomes would be well predicted by birth weight-discordant when the diagnostic cut-off of ΔBW was 12%-17%, with an acceptable sensitivity (0.53-0.78) and a high specificity (0.72-0.79). Conclusions: Birth weight discordant is not uncommon in live-born twins, and is associated with adverse outcomes including ELBW, SGA, and transferring to the department of neonatology in the small twins. Besides, the risk is linearly related to the increase of ΔBW. In the future, more researches are needed to explore the underline mechanism and long-term impact of birth weight discordance, to guide the prevention and management.
Birth Weight ; Female ; Fetal Growth Retardation ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Male ; Pregnancy ; Premature Birth/epidemiology* ; Retrospective Studies ; Twins

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29⁺⁵ to 40⁺⁴ weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.
Child ; Female ; Fetal Growth Retardation ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Placenta ; Placenta Diseases ; Pregnancy ; Retrospective Studies