Ozone (O3) pollution is increasingly recognized as a serious environmental threat associated with elevated dementia risks. However, evidence regarding the impact of prenatal exposure to O3 on the morphological development of the brain remains limited. This nationwide population-based study investigated associations between prenatal O3 exposure and brain volume in 3294 infants aged 0-1 year without major anomalies, who underwent magnetic resonance imaging for non-neurological indications at hospitals within the China Neonatal Neuro-Critical Care Network group. Prenatal O3 exposure was estimated using geocoded residential addresses linked to 1 km × 1 km air pollution datasets. Linear mixed-effects models revealed that each 10 μg/m3 increase in prenatal O3 exposure was associated with a decrease of 1.14% (95% CI: 0.38-1.88) in total brain volume, 1.15% (95% CI: 0.40-1.89) in gray matter volume, 1.13% (95% CI: 0.37-1.88) in white matter volume, 1.11% (95% CI: 0.35-1.87) in cerebral blood volume, and 1.12% (95% CI: 0.36-1.88) in cerebrospinal fluid. No significant association was observed for the apparent diffusion coefficient [-0.08% (95% CI: -0.43-0.27)]. The associations remained significant in dual-pollutant models that additionally adjusted for prenatal PM2.5 exposure. Mediation analysis confirmed a direct effect of prenatal O3 exposure on brain morphology, as birth weight accounted for only 3.47% to 3.54% of the total effect. Our findings underscore the imperative for stricter air quality regulations to protect pregnant individuals and mitigate potential neurodevelopmental impairment originating as early as the fetal stage.

Next-generation sequencing technologies have been widely applied in diagnosing genetic disorders in pediatric patients. However, the cancer predisposition and tumor characteristics in individuals who have germline pathogenic variants remain unclear. We analyzed exome sequencing data from 75,602 pediatric patients referred for genetic testing between January 2016 and January 2025, tracking cancer as a secondary finding. The most common reasons for genetic testing were symptoms related to the nervous system, metabolic disorders and immune dysfunction. Among 110,692 variants of 139 tumor susceptibility genes, we identified 501 (456 single-nucleotide variants, 45 copy number variations, 0.45%) pathogenic or likely pathogenic (P/LP) and 3,848 (3,650 single-nucleotide variants, 198 copy number variations, 3.5%) variants of uncertain significance leaning toward likely pathogenic variants. Of 411 patients with tumors (203 with preexisting tumors and 208 with new tumors diagnosed during follow-up), 134 (32.6%) harbored causative germline P/LP variants in genes such as NF1 (13.1%), TSC2 (5.8%), RB1 (4.6%) and WT1 (3.2%). Critically, prospective follow-up of 64,187 patients without initial tumors revealed a significantly higher incidence of malignant tumors in those carrying P/LP variants (3.23 per 1,000 person-years) compared with those with variants of uncertain significance leaning toward likely pathogenic or other variants (0.236 and 0.272 per 1,000 person-years, respectively). These findings underscore the importance of proactive genetic counseling and surveillance for pediatric patients with pathogenic germline variants.

Background Intracranial hemorrhage (IVH) and periventricular leukomalacia (PVL) are common complications in preterm infants with a gestational age (GA) < 32 weeks. Severe IVH (Grades 3–4) and PVL can lead to long-term neurological sequelae, including cerebral palsy, epilepsy, and intellectual disabilities. The safety and efficacy of inhaled nitric oxide (iNO) in infants with GA < 32 weeks remains controversial. Some studies suggest that iNO can improve oxygenation but may affect coagulation and increase the risk of IVH. Objective This study aimed to identify the factors influencing the occurrence of severe brain injury (sBI) in preterm infants with GA < 32 weeks receiving iNO treatment, using propensity score matching (PSM) analysis. Methods A multicenter retrospective cohort study was conducted, including preterm infants born at GA < 32 weeks who received iNO treatment for more than 3 hours across eight hospitals in China between 2013 and 2022. Infants were divided into two groups based on the occurrence of sBI. PSM was used to match the infants in a 1:1 ratio based on covariates such as GA, birth weight, and gender. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for sBI. Repeated-measures ANOVA and mediation analysis were used to assess the significance of risk factors and their potential mediating effects on the occurrence of sBI. Results After matching, baseline characteristics between the sBI and non-sBI groups were balanced. Univariate and multivariate analyses showed that reduced platelet count was an independent risk factor for sBI. The total invasive high-frequency mechanical ventilation time, P/F ratio at 3 hours and 6 hours post-iNO treatment were statistically significant in univariate analysis but not in multivariate analysis. Mediation analysis revealed no mediating effect of mechanical ventilation time or P/F ratio on the relationship between platelet count and sBI. Repeated-measures ANOVA showed that iNO treatment significantly affected the P/F ratio, which improved over time. However, no significant difference in P/F ratio changes was observed between the sBI and non-sBI groups. Conclusion This study suggests that reduced platelet count is an independent risk factor for the occurrence of sBI in preterm infants with GA < 32 weeks receiving iNO treatment. Although total invasive high-frequency mechanical ventilation time and P/F ratio changes may also affect sBI occurrence, they do not mediate the relationship between platelet count and sBI.

BACKGROUND:Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship. OBJECTIVE:To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids. METHODS:Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM. RESULTS:Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk. CONCLUSIONS:Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this.

To analyse early risk factors for mortality in preterm infants treated with inhaled nitric oxide (iNO) in China. A retrospective observational case-control study. 8 tertiary hospitals in 5 regions of China. 726 preterm infants treated with iNO for hypoxic respiratory failure or persistent pulmonary hypertension of newborns. None. The primary outcome was survival status at discharge. (1) The mortality rate was 27.1% (197/726), and which significantly reduced with increasing gestational age (GA) and birth weight. (2) Compared with the survival group, the death group had significantly greater use of assisted reproductive technology, higher multiple pregnancy rates and lower caesarean section rates. Infants in the death group had a significantly higher incidence of small for GA (SGA), Apgar score ≤3 at 1 min after birth, pneumorrhagia, sepsis and shock. In the death group, the utilisation rate of a pulmonary surfactant (PS) was significantly lower, whereas the oxygenation index (OI) before iNO treatment was significantly higher. The maximum dose of iNO in the death group was significantly higher than that in the survival group. (3) The Cox proportional hazard model showed that SGA (HR 1.800, 95% CI (1.113 to 2.911)), sepsis (HR 1.488, 95% CI (1.093 to 2.027)), shock (HR 1.473, 95% CI (1.033 to 2.100)), OI before iNO treatment (HR 1.016, 95% CI (1.006 to 1.026)) and the maximum dose of iNO treatment (HR 1.070, 95% CI (1.035 to 1.105)) were risk factors for death in preterm infants treated with iNO. Furthermore, GA (HR 0.876, 95% CI (0.831 to 0.924)), PS (HR 0.433, 95% CI (0.296 to 0.633)) and a higher initial dose of iNO (HR 0.926, 95% CI (0.891 to 0.962)) were identified as protective factors. (4) Stratified analysis and sensitivity analysis determined the stability of the core results in preterm infants with GA between 28 and 36+6 weeks. Premature infants treated with iNO had a high mortality rate. SGA, sepsis, shock and higher OI before iNO treatment increased the mortality risk in infants with GA between 28 and 36+6 weeks. A higher GA the use of PS, and a higher initial iNO dose could improve the survival outcome of these babies. The study was registered in the Chinese Clinical Trials Registry (http://www.chictr.org.cn; registration number: ChiCTR2200066935).

Despite the lack of consensus, the use of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) of less than 34 weeks has been increasing in recent years. At present, there are no multi-center studies in China on the use of iNO in this population. This study aims to investigate the use of iNO in preterm infants under 34 weeks of gestation over the past 10 years in China, and provides evidence-based medical proof for the use of iNO in these neonates. Using a retrospective study method, clinical data were collected from infants with a GA of less than 34 weeks who received iNO therapy in the neonatal units of five tertiary hospitals in China from January 2013 to December 2022. The infants were divided into two groups: Group A (2013–2017) and Group B (2018–2022). The differences in clinical characteristics, iNO use, and short-term outcomes between the two groups were analyzed. Over the past decade, the use of iNO in preterm infants with a GA of less than 34 weeks has increased gradually, with a more pronounced rise in its use among preterm infants born at 24–27 weeks. The proportion of infants receiving iNO therapy has increased from 1.23

This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China.The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups.Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05).Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.

ObjectiveThis study aimed to investigate the association between antimony (Sb) exposure and glycated hemoglobin (HbA1c) levels in adolescents.MethodsA cross-sectional study of 751 adolescents aged 12–19 years was conducted via the National Health and Nutrition Examination Survey (NHANES, 2013–2016). Survey-weighted linear regression and restricted cubic spline (RCS) analyses were applied to evaluate the relationship of urinary Sb exposure with HbA1c.ResultsA significant relationship was observed between urinary Sb concentrations and HbA1c levels (percent change: 0.93; 95% CI: 0.42, 1.45) after full adjustment. After converting urinary Sb levels to a categorical variable by tertiles (T1–T3), the highest quantile was associated with a significant increase in HbA1c (percent change: 1.45; 95% CI: 0.38, 2.53) compared to T1. The RCS models showed a monotonically increasing relationship of urinary Sb with HbA1c. Subgroup analyses revealed a sex-specific relationship between urinary Sb exposure and HbA1c with a significant positive association in males and a non-significant positive association in females. Sensitivity analyses further confirmed the relationship between urinary Sb and HbA1c, even after excluding participants who were overweight or obese (percent change: 1.58%, 95% CI: 0.88, 2.28) and those with serum cotinine levels ≥ 1 ng/mL (percent change: 1.14%, 95% CI: 0.49, 1.80).ConclusionOur findings indicated that increased Sb exposure may correlate with higher HbA1c levels, especially in male adolescents. More studies are needed to further explore and validate the potential mechanisms.

BackgroundBronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated.ObjectiveTo assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM).MethodsWe conducted a retrospective cohort study of infants born at 22–32 weeks gestation with PPHN or HRF, treated with iNO for over 3 h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI).ResultsA higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (adjusted OR = 0.68, 95% CI: 0.52–0.89, p < 0.01). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI.ConclusionA higher initial iNO dose within the first 7 days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.

ObjectiveThis study aimed to develop and validate a model for predicting extrauterine growth restriction (EUGR) in preterm infants born ≤34 weeks gestation.MethodsPreterm infants from Guangxi Maternal and Child Health Hospital (2019–2021) were randomly divided into training (80%) and testing (20%) sets. Collinear clinical variables were excluded using Pearson correlation coefficients. Predictive factors were identified using Lasso regression. Random forest (RF), support vector machine (SVM), and logistic regression (LR) models were then built and evaluated using the confusion matrix, area under the curve (AUC), and the F1 score. Additionally, calibration curves and decision curve analysis (DCA) were plotted to assess the performance and practical utility of the models.ResultsThe study included 387 infants, with no significant baseline differences between training (n = 310) and testing (n = 77) sets. LR identified gestational age, birth weight, premature rupture of membranes, patent ductus arteriosus, cholestasis, and neonatal sepsis as key EUGR predictors. The RF model (19 variables) demonstrated an accuracy of greater than 90% during training, and superior AUC (0.62), F1 score (0.80), and accuracy (0.72) in testing compared to other models.ConclusionsGestational age, birth weight, premature rupture of membranes, patent ductus arteriosus, cholestasis, and neonatal sepsis are significant EUGR predictors in preterm infants ≤34 weeks. The model shows promise for early EUGR prediction in clinical practice, potentially enhancing screening efficiency and accuracy, thus saving medical resources.

Objective: To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes. Methods: A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups. Results: The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001). Conclusion: The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.

Introduction:Early identification and intervention of neurodevelopmental impairment in preterm infants may significantly improve their outcomes. This study aimed to build a prediction model for short-term neurodevelopmental impairment in preterm infants using machine learning method. Methods:Preterm infants with gestational age  < 32 weeks who were hospitalized in The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, and were followed-up to 18 months corrected age were included to build the prediction model. The training set and test set are divided according to 8:2 randomly by Microsoft Excel. We firstly established a logistic regression model to screen out the indicators that have a significant effect on predicting neurodevelopmental impairment. The normalized weights of each indicator were obtained by building a Support Vector Machine, in order to measure the importance of each predictor, then the dimension of the indicators was further reduced by principal component analysis methods. Both discrimination and calibration were assessed with a bootstrap of 505 resamples. Results:In total, 387 eligible cases were collected, 78 were randomly selected for external validation. Multivariate logistic regression demonstrated that gestational age(p = 0.0004), extrauterine growth restriction (p = 0.0367), vaginal delivery (p = 0.0009), and hyperbilirubinemia (0.0015) were more important to predict the occurrence of neurodevelopmental impairment in preterm infants. The Support Vector Machine had an area under the curve of 0.9800 on the training set. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the curve on the test set is 0.70. The external validation proves the reliability of the prediction model. Conclusion:A support vector machine based on perinatal factors was developed to predict the occurrence of neurodevelopmental impairment in preterm infants with gestational age  < 32 weeks. The prediction model provides clinicians with an accurate and effective tool for the prevention and early intervention of neurodevelopmental impairment in this population.

OBJECTIVES:To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI.METHODS:In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups.RESULTS:Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05).CONCLUSIONS:There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

Objectives Neonatal necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that primarily affects preterm and very low birth weight infants, with high morbidity and mortality. We aim to build a reliable prediction model to predict the risk of NEC in preterm and very low birth weight infants. Methods We conducted a retrospective analysis of medical data from infants (gestational age <32 weeks, birth weight <1,500 g) admitted to Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. We collected clinical data, randomly dividing it into an 8:2 ratio for training and testing. Multivariate logistic regression was employed to identify significant predictors for NEC. Principal component analysis was used for dimensionality reduction of numerical variables. The prediction model was constructed through logistic regression, incorporating all relevant variables. Subsequently, we calculated performance evaluation metrics, including Receiver Operating Characteristic (ROC) curves and confusion matrices. Additionally, we conducted model performance comparisons with common machine learning models to establish its superiority. Results A total of 292 infants were included, with 20% ( n = 58) randomly selected for external validation. Multivariate logistic regression revealed the significance of four predictors for NEC in preterm and very low birth weight infants: temperature ( P = 0.003), Apgar score at 5 min ( P = 0.004), formula feeding ( P = 0.007), and gestational diabetes mellitus (GDM, P = 0.033). The model achieved an accuracy of 82.46% in the test set with an F1 score of 0.90, outperforming other machine learning models (support vector machine, random forest). Conclusions Our logistic regression model effectively predicts NEC risk in preterm and very low birth weight infants, as confirmed by external validation. Key predictors include temperature, Apgar score at 5 min, formula feeding, and GDM. This study provides a vital tool for NEC risk assessment in this population, potentially improving early interventions and child survival. However, clinical validation and further research are necessary for practical application.

Primary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of free carnitine from mothers may cause false negatives or positives during newborn screening (NBS). This study aimed to analyze the genetic characteristics of SLC22A5 and estimate the prevalence of PCD in the Chinese population, providing useful information for NBS and genetic counseling. We manually curated SLC22A5 pathogenic or likely pathogenic (P/LP) variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines and identified 128 P/LP variants. Based on the China Neonatal Genomes Project (CNGP), the estimated PCD prevalence was 1:17,456, which was higher than that in other populations. The genotype–phenotype association analysis showed that patients carrying homozygous c.760C>T and c.844C>T were more likely to present cardiomyopathy, whereas those carrying homozygous c.1400C>G were more likely to be asymptomatic (all p-values < 0.05). We found that there was no significant difference in initial C0 concentrations between patients and carriers, but there was a significant difference in the second-tier screening of C0 concentration between them (p-value < 0.05). We established a cost-effective variant panel containing 10 high-frequency sites and developed a screening algorithm incorporating gene panels with MS/MS, which could rescue one more patient who was undetected from MS/MS. In conclusion, the prevalence of PCD in the Chinese population is relatively high. The combination of conventional NBS with genetic sequencing is suggested for early diagnosis of PCD.

Importance A growing number of children are conceived with assisted reproductive technology (ART). However, there is a lack of studies systematically analyzing the genetic landscape of live-born children conceived through ART who need intensive care in the neonatal period. Objective To investigate the incidence and type of molecular defects among neonates conceived through ART who are in intensive care units (NICUs) with suspected genetic conditions. Design, Setting, and Participants This was a cross-sectional study using data from the China Neonatal Genomes Project, a multicenter national neonatal genome data set managed by the Children’s Hospital of Fudan University. All participants were from level III and IV NICUs and included 535 neonates conceived through ART with suspected genetic conditions, with data collected between August 1, 2016, and December 31, 2021, and 1316 naturally conceived neonates with suspected genetic conditions in the same clinical settings, with data collected between August 1, 2016, and December 31, 2018. The data were analyzed between September 2021 and January 2023. Exposures Whole-exome sequencing or target clinical exome sequencing with pathogenic or likely pathogenic single-nucleotide variant (SNV) and copy number variation (CNV) detection was performed for each individual. Main Outcomes and Measures The primary outcome was the molecular diagnostic yield, mode of inheritance, spectrum of genetic events, and incidence of de novo variants. Results A total of 535 neonates conceived through ART (319 boys [59.6%]) and 1316 naturally conceived neonates (772 boys [58.7%]) were included. A genetic diagnosis was established for 54 patients conceived through ART (10.1%), including 34 patients with SNVs (63.0%) and 20 with CNVs (37.0%). In the non-ART group, 174 patients (13.2%) received a genetic diagnosis, including 120 patients with SNVs (69.0%) and 54 with CNVs (31.0%). The overall diagnostic yield was comparable between the ART group and the naturally conceived neonates (10.1% vs 13.2%; odds ratio [OR], 0.74; 95% CI, 0.53-1.02), as was the proportion of SNVs (63.0% vs 69.0%; OR, 0.68; 95% CI, 0.46-1.00) and CNVs (37.0% vs 31.0%; OR, 0.91; 95% CI, 0.54-1.53) detected by sequencing. Furthermore, the proportions of de novo variants in the ART group and the non-ART group were similar (75.9% [41 of 54] vs 64.4% [112 of 174]; OR, 0.89; 95% CI, 0.62-1.30). Conclusions and Relevance This cross-sectional study of neonates in NICUs suggests that the overall genetic diagnostic yield and the incidence of de novo variants were similar between live-born neonates conceived through ART and naturally conceived neonates in the same settings.

Objective:To study the clinical characteristics and differences between clinical subtypes of neonates with SARS-CoV-2 infection.Methods:From December 11, 2022 to January 10, 2023, neonates with SARS-CoV-2 infection admitted to our hospital were retrospectively studied. The neonates were assigned into two groups according to the clinical classification: the mild group (including asymptomatic, mild and moderate disease) and the severe group (including severe and critical disease). The clinical characteristics were summarized and compared between the groups.Results:Among 162 confirmed cases, 91 (56.2%) were male, 27 (16.7%) were preterm infants and 26 (16.0%) were low birth weight infants (LBWIs). The average age of onset was 15(8,21)d with 125 cases (77.2%) had onset after 7 d of birth. The main clinical manifestations included fever (79.0%), cough (59.3%) and nasal congestion (42.6%). 70 cases (43.2%) had abnormal complete blood count (CBC) with neutropenia most common. 136 cases (84.0%) were in the mild group and 26 in the severe group. The severe group showed higher proportion of male, preterm and LBWIs than the mild group ( P<0.05). The most common clinical manifestation was fever in the mild group and cyanosis in the severe group. Compared with the mild group, the severe group had higher incidence of poor response and longer duration of fever ( P<0.05). No significant difference existed in CBC between the two groups ( P>0.05). 127 neonates received chest X-ray and 77(60.6%) showed pneumonia. 157 neonates were discharged with improvement or full-recovery. The length of hospital stay was 5(3,6)d. 5 patients were discharged refusing further treatment. Conclusions:Most SARS-CoV-2 infections in neonates are mild and moderate types with mild symptoms and fever. A few are severe or critical types with cyanosis the most common symptom. Neonates with poor responses and prolonged fever need to be alerted to the possibility of severe disease, especially for male, preterm and LBWIs. Most neonates have a favorable prognosis.

IMPORTANCE Neonatal seizures pose a significant challenge in critical care, and continuous video electroencephalography (cEEG) monitoring holds promise for early detection of seizures. However, large-scale data on the incidence of neonatal seizures and monitoring systems in China are lacking. OBJECTIVES To determine the incidence of neonatal seizures in infants with high risk in China. DESIGN, SETTING, AND PARTICIPANTS A large, cross-sectional multicenter study was conducted from January 2017 to December 2018 in the neonatal intensive care units (NICUs) of 7 tertiary medical centers in China. Neonates with high risk were included, and cEEG monitoring was conducted. Data were collected between January 1, 2017, and January 31, 2020. The data were analyzed between January 2021 and January 2022. MAIN OUTCOMES AND MEASURES The incidence of neonatal seizures, categorized by etiology, and seizure burden. RESULTS A total of 20 310 neonates with high risk were included (10 495 [51.7%] male; mean [SD] postmenstrual age, 37.7 [3.7] weeks), and seizures were observed in 3423 infants (16.9%). The highest proportion of seizures was attributed to acute neonatal encephalopathy (1448 [42.3%]). The incidence of seizures decreased with postmenstrual age and birth weight, with the highest occurrence observed in neonates with postmenstrual age of less than 28 weeks (237 of 879 [27.0%]) or birth weight of less than 1.0 kg (269 of 914 [29.4%]). Preterm infants had a higher proportion of moderate and severe seizure burdens compared with full-term infants (moderate severity: 248 of 1199 [20.7%] vs 454 of 2224 [20.4%]), but no significant differences were observed in etiology. Seizure burden was highest with genetic syndromes (49 of 188 [26.1%]), central nervous system malformations (33 of 127 [26.0%]), and inborn errors of metabolism (27 of 113 [23.9%]). During hospitalization, 7.8% of neonates with seizures died (267 neonates), with 81.3% of these cases having a moderate or severe seizure burden (217 neonates). Mortality was generally higher in preterm vs full-term infants (98 of 1199 [8.2%] vs 169 of 2224 [7.6%]) and increased with the severity of seizure burden (217 of 267 neonates with moderate or severe burden [81.3%]). CONCLUSIONS AND RELEVANCE This cross-sectional study of neonatal seizures underscores the substantial burden seizures pose to high-risk infants with brain injury in China, particularly those who are born prematurely or who have congenital conditions.

OBJECTIVE Bronchopulmonary dysplasia (BPD) is one of the most serious complications affecting extremely preterm infants. We aimed to evaluate temporal trends in BPD and administration of respiratory support among extremely preterm infants in China over a decade. METHODS This was a retrospective study using data from a multicenter database, which included infants born less than 28 weeks' gestation discharged from 68 tertiary neonatal care centers in China between 2010 and 2019. Changes in rates and severity of BPD, as well as modalities and duration of respiratory support, were evaluated. RESULTS Among 4808 eligible infants with gestational age (GA) of 21+6/7  to 27+6/7 weeks and a mean (SD) birth weight of 980 (177) g, no significant change of median GA was found over time. Overall, 780 (16.2%) infants died before 36 weeks' postmenstrual age, 2415 (50.2%) were classified as having no BPD, 917 (19.1%) developed Grade 1 BPD, 578 (12.0%) developed Grade 2 BPD, and 118 (2.5%) developed Grade 3 BPD. The rate of BPD increased from 20.8% in 2010 to 40.7% in 2019 (aRR for trend, 1.081; 95% confidence interval, 1.062-1.099), especially for Grade 1 and Grade 2. Although survival to discharge improved over the decade, the overall survival without BPD did not change during the study period. The use of invasive mechanical ventilation (IMV) remained unchanged. However, the use of noninvasive ventilation (NIV) increased from 71.5% in 2010 to 89.8% in 2019. Moreover, the median duration of NIV increased over time, from 17.0 (4.8, 34.0) days in 2010 to 33.0 (21.0, 44.0) days in 2019, without significant change in the duration of IMV. CONCLUSIONS Although survival increased over the decade and respiratory support practices changed significantly between 2010 and 2019 in China, with increased use and duration of NIV, there was an increased rate of BPD and survival without BPD has not improved.

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) corresponds to a spectrum of defects. Several large-cohort studies have used high-throughput sequencing to investigate the genetic risk of CAKUT during antenatal, childhood, and adulthood period. However, our knowledge of newborns with CAKUT is limited.Methods: This multicenter retrospective cohort study explored the genetic spectrum of CAKUT in a Chinese neonatal cohort. Clinical data and whole exome sequencing (WES) data of 330 newborns clinically diagnosed with CAKUT were collected. WES data were analyzed for putative deleterious single nucleotide variants (SNVs) and potential disease-associated copy number variants (CNVs).Results: In this study, pathogenic variants were identified in 61 newborns (18.5%, 61/330), including 35 patients (57.4%) with SNVs, 25 patients (41%) with CNVs, and 1 patient with both an SNV and a CNV. Genetic diagnosis rates were significantly higher in patients with extrarenal manifestations (P<0.001), especially in those with cardiovascular malformations (P<0.05). SNVs in genes related to syndromic disorders (CAKUT with extrarenal manifestations) were common, affecting 20 patients (57.1%, 20/35). KMT2D was the most common gene (5 patients) and 17q12 deletion was the most common CNV (4 pa-tients). Patient 110 was detected with both a CNV (17q12 deletion) and an SNV (a homozygous variant of SLC25A13). Among the newborns with positive genetic results, 22 (36.1%, 22/61) patients may benefit from a molecular diagnosis and change in clinical management (including early multidisciplinary treatment, disease-specific follow-up, and familial genetic counseling).Conclusion: This study shows the heterogeneous genetic etiologies in a Chinese CAKUT neonatal cohort by using WES. Patients with CAKUT who have extrarenal manifestations are more likely to harbor genetic diagnoses. Kabuki syndrome and 17q12 deletion syndrome were the most common genetic findings. Approximately 36.1% of the patients may benefit from molecular diagnoses and a change in clinical management.