Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome.

Introduction: The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. Methods: A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Results: Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P < 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Conclusion: Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

Pathogen-specific alterations in intestinal microbiota precede urinary tract infections in preterm infants: a longitudinal case-control study.

Urinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

Temporal trend in mortality due to congenital heart disease in China from 2008 to 2021.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS: CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.

Associations of Early Gut Microbiome and Metabolome with Growth and Body Composition of Preterm Infants Within the First 6 Months.

Objectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Critical windows of greenness exposure during preconception and gestational periods in association with birthweight outcomes.

Few studies have examined the association between greenness exposure and birth outcomes. This study aims to identify critical exposure time windows during preconception and pregnancy for the association between greenness exposure and birth weight. A cohort of 13 890 pregnant women and newborns in Shanghai, China from 2016-2019 were included in the study. We assessed greenness exposure using Normalized Difference Vegetation Index (NDVI) during the preconception and gestational periods, and evaluated the association with term birthweight, birthweight z-score, small-for-gestational age, and large-for-gestational age using linear and logistic regressions adjusting for key maternal and newborn covariates. Ambient temperature, relative humidity, ambient levels of fine particles (PM2.5) and nitrogen dioxide (NO2) assessed during the same period were adjusted for as sensitivity analyses. Furthermore, we explored the potential different effects by urbanicity and park accessibility through stratified analysis. We found that higher greenness exposure at the second trimester of pregnancy and averaged exposure during the entire pregnancy were associated with higher birthweight and birthweight Z-score. Specifically, a 0.1 unit increase in second trimester averaged NDVI value was associated with an increase in birthweight of 10.2 g (95% CI: 1.8-18.5 g) and in birthweight Z-score of 0.024 (0.003-0.045). A 0.1 unit increase in an averaged NDVI during the entire pregnancy was associated with 10.1 g (95% CI: 1.0-19.2 g) increase in birthweight and 0.025 (0.001-0.048) increase in birthweight Z-score. Moreover, the associations were larger in effect size among urban residents than suburban residents and among residents without park accessibility within 500 m compared to those with park accessibility within 500 m. Our findings suggest that increased greenness exposure, particularly during the second trimester, may be beneficial to birth weight in a metropolitan area.

Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

BACKGROUND: As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. OBJECTIVE: This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. METHODS: This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. RESULTS: In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). CONCLUSIONS: Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

Trajectory of stratum corneum lipid subclasses in the first year of life and associations with atopic dermatitis: A prospective cohort study.

BACKGROUND: Trajectories of stratum corneum (SC) lipid subclasses and their associations with infant atopic dermatitis (AD) are unclear. This study aimed to quantify the trajectories of 15 SC subclasses and carbon chain lengths and their associations with AD within 12 months. METHODS: In total, 213 newborns were enrolled at birth with nonlesional skin samples collected from the inner forearm at birth, 42 days, 3, 6, and 12 months, respectively. Lesional skin samples were collected from 120 AD patients at clinic with the disease onset within the first year of life. Mass spectrometry was applied to assess relative contents of 12 ceramide (CER), three free fatty acid (FFA) subclasses, and average carbon chain length (CCL). AD incident within 1 year old was diagnosed by dermatologists according to UK criteria. RESULTS: Sixty-four (30.0%) cases of ADs occurred in the cohort. All SC lipid subclasses and CCLs, but EOP varied significantly during the first year. AD infants showed lower NP but higher NS, NH, AP, hydroxy FFA, and CCL of FFAs compared with nonaffected infants. After normalization by age, the differences remained and were more pronounced in lesional skin of clinical AD infants compared with non-ADs. NS, NH, and CCL of FFAs in lesional skin of AD infants showed positive and significant correlations with the levels of transepidermal water loss at 3 month; some evidence supports a negative correlation for NP. CONCLUSIONS: We provide an overview of developmental trajectories of 15 CER and FFA subclasses across the first year of healthy infants and a link between the imbalance of some subclasses with the development of AD.

Dynamics and Crosstalk between Gut Microbiota, Metabolome, and Fecal Calprotectin in Very Preterm Infants: Insights into Feeding Intolerance.

BACKGROUND: Feeding intolerance (FI) is a significant concern in the care of preterm infants, impacting their growth and development. We previously reported that FI is linked to lower fecal calprotectin (FC) levels. This study aims to explore the postnatal dynamics and interplay between microbiota, metabolic profiles, and host immunity in preterm infants with and without FI. METHODS: Infants with gestational age <32 weeks or birth weight <1500 g were enrolled at the Children's Hospital of Fudan University between January 2018 and October 2020. Weekly fecal samples were analyzed for bacterial profiling, metabolome, and calprotectin levels, exploring their longitudinal development and interrelationships. RESULTS: Of the 118 very preterm infants studied, 48 showed FI. These infants experienced an interrupted microbial-immune trajectory, particularly at 3-4 weeks of age, marked by a reduced bacterial abundance, alpha diversity, and FC levels. Metabolic changes in FI were pronounced between 3 and 6 weeks. Pantothenic acid and two polyamine metabolites were closely associated with bacterial abundance and FC levels and negatively correlated with the duration to attain full enteral feeding. CONCLUSIONS: FI infants demonstrated compromised microbiome-immune interactions, potentially influenced by specific metabolites. This research underscored the importance of early microbial and metabolic development in the pathogenesis of FI in very preterm infants.

Effect of wearing peripheral focus-out glasses on emmetropization in Chinese children aged 6-8 years: study protocol for a 2-year randomized controlled intervention trial.

BACKGROUND: Myopia is one of the most common eye diseases causing visual impairment and blindness, and the high prevalence in adolescents remains a major public health concern. Based on clinical studies using optical defocus to regulate ocular growth and refractive changes through visual feedback, we hypothesize that early wearing of peripheral myopic defocusing spectacles in children with high risk of myopia may slow the process of emmetropization and even prevent the onset of myopia by inducing more peripheral myopic defocus. The aim of this study is to investigate whether the wearing of peripheral focus-out glasses can be effective in delaying emmetropization in non-myopic children aged 6-8 years. METHODS: The study is a 2-year randomized controlled trial. A total of 160 subjects will be randomized into the experimental group or the control group. The experimental group will be fitted with direct emmetropia with focus-out glasses (DEFOG) to guide the emmetropization process. The control group will not receive any treatment and will serve as a blank control group. The primary aim is to determine whether non-myopic children wearing DEFOG lenses are superior to those who do not receive any intervention on the progression of cycloplegic objective refraction over 2 years. DISCUSSION: This is the first randomized controlled trial aiming at myopic prevention by non-invasive intervention in non-myopic children. This study aims to initially investigate whether wearing peripheral focus-out glasses can effectively delay the process of emmetropization in children aged 6-8 years with high risk of myopia, which might give potential clues for further exploration on early prevention of myopia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05689567. Registered on 10 January 2023.

Identifying critical windows of air pollution exposure during preconception and gestational period on birthweight: a prospective cohort study.

BACKGROUND: Few studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods. METHODS: Leveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016-2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children's sex-specific associations were explored. RESULTS: After controlling for covariates, one standard deviation (SD) (11.5 µg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 - 26%) and 14% (95% CI: 1 - 29%) increase in SGA, respectively; and one SD (9.6 µg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 - 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22-32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found. CONCLUSION: Consistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial.

BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.

Intermittent dietary carbohydrate restriction versus calorie restriction and cardiometabolic profiles: A randomized trial.

OBJECTIVE: The aim of this study was to investigate the effectiveness of an intermittent low-carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and potential mechanisms. METHODS: Thirty-four participants aged 9 to 30 years with cardiometabolic risk were randomized to receive a self-administered 2-week ILCD (carbohydrate intake ≤ 50 g/d on seven nonconsecutive days) or ICR (500-600 kcal/d for two consecutive days per week). Differences in changes in obesity measures, glycemic and lipid profiles, gut microbiota composition, and three serum biomarkers were compared. RESULTS: The ILCD and ICR similarly reduced body weight, waist circumference, fasting glucose, insulin, postprandial glucose variation, monocyte chemoattractant protein-1, free fatty acid, and fibroblast growth factor 21, whereas ILCD produced significantly different alterations in the following outcomes compared with ICR: greater increases in low-density lipoprotein cholesterol and total cholesterol (-0.36 mmol/L, 95% CI: -0.68 to -0.04; -0.40 mmol/L, 95% CI: -0.73 to -0.06) and greater decrease in triglyceride (0.20 mmol/L, 95% CI: 0.04 to 0.37). Actinobacteria and Bifidobacterium reduced after ILCD but not ICR; and the reductions strongly correlated with changes in fasting glucose (both r = 0.84) and low-density lipoprotein cholesterol (r = -0.81 and -0.72). CONCLUSIONS: This study found no evidence of differences in changes from baseline in obesity measures, glucose regulation, and inflammation between ILCD and ICR, despite trends in reduction in those parameters. However, there seemed to be some differences in responses in lipids and gut microbiota.

Analysis of the CHD7 gene mutations in patients of congenital heart disease with extracardiac malformations.

Background: Congenital heart disease (CHD) is a common birth defect, and is frequently accompanied with extracardiac malformations (ECM). Uncovering the genetic etiology of CHD may have a meaningful impact on disease management. De novo variants have been proven to be associated with CHD. Methods: Whole exome sequencing was performed for 4 unrelated CHD families with extracardiac malformations, candidate genes were screened by using stringent bioinformatics analysis, and the obtained variants were confirmed by Sanger sequencing. RT-PCR and Sanger sequencing were used to investigate the influence of a splice variant on pre-mRNA splicing. Further targeted sequencing was conducted to investigate the association of CHD7 variants with sporadic CHD. Results: Four novel heterozygous loss-of-function CHD7 mutations were found by using stringent bioinformatics analysis: the frameshift mutation c.1951_1952delAAinsT (p.L651X) in family #1, the nonsense mutations c.2913C>G (p.Y971X) in family #2 and c.3106C>T (pA1036X) in family #3, and the splicing mutation c.4353+4_4353+12delinsGCCCA in family #4. Sanger sequencing confirmed that these were all de novo mutations and were absent in the healthy parents and siblings of the probands. Further studies revealed that the splice mutation c.4353+4_4353+12delinsGCCCA influenced CHD7 mRNA splicing in vivo. Targeted sequencing found 23 rare mutations in 1,155 sporadic CHD patients. Conclusions: The findings here confirm that de novo loss-of-function variants of the CHD7 gene are the genetic cause of familial CHD with extracardiac malformations and the spectrum of pathogenic CHD7 variants in sporadic CHD is expanded.

Impact of Newborn Screening Programme for Congenital Heart Disease in Shanghai: a five-year observational study in 801,831 newborns.

Background: Newborn Screening Programme for Congenital Heart Disease (CHD) in Shanghai has been in operation for over 5 years, and its feasibility and effectiveness still lack a systematic and comprehensive evaluation. This study aimed to detail the implementation of the programme and evaluate its results, benefits, and reliability in clinical practice. Methods: This study was an observational study involving all newborns received CHD screening in Shanghai from 2017 to 2021. Pulse oximetry (POX) plus cardiac murmur auscultation (namely the dual-index method) was used for CHD screening in newborns aged 6-72 h. Newborns who screened positive was recommended for echocardiography, and those diagnosed with CHD would be planned for further evaluation and intervention. Data were aggregated by birth year and district of birth. Results of neonatal CHD screening, diagnosis and treatment, and temporal trends of infant mortality rate (IMR) and the proportion of under-five mortality (U5M) attributed to CHD were analysed. A retrospective cohort study was also conducted to assess the reliability of the dual-index method in clinical practice. Findings: In total, 801,831 (99.48%) newborns were screened for CHD, 16,489 (2.06%) were screened positive, and 3541 (21.47%) of the screened-positive newborns were identified with CHD. Seven hundred and fifty-two patients with CHD received surgical or interventional treatment with a successful rate of 94.81%. The period from 2015 to 2021 witnessed an approximately twofold decrease in IMR from 4.58‰ to 2.30‰, and a downtrend in the proportion of U5M attributed to CHD from 25.93% to 16.61%. High sensitivity and specificity of the dual-index method in clinical practice were observed for both critical (100.00% and 97.72%) and major CHD (98.47% and 97.76%). Interpretation: Newborn screening programme for CHD has been well implemented in Shanghai, and this programme is a successful public health intervention to reduce infant death. Our study provides encouraging evidence and experience for implementing newborn screening programme for CHD nationwide in China. Funding: This study was supported by the National Key Research and Development Programme of China (2021YFC2701004 and 2016YFC1000506), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-002), and Three-Year Planning for Strengthening the Construction of Public Health System in Shanghai (No. GWIV-24).

Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections.

OBJECTIVES: To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. METHODS: This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015-2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. RESULTS: Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. CONCLUSIONS: Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Comparison of biochemical characteristics and gel properties of chicken myofibrillar protein affected by heme-iron and nonheme-iron oxidizing systems.

In this study, the effect of hemin and non-heme iron on the biochemical and gelling properties of chicken myofibrillar protein (MP) was compared. Results revealed that free radicals from hemin incubated MP were significantly higher than that in FeCl3 incubated samples (P < 0.05), and had higher ability to initiate protein oxidation. The carbonyl content, surface hydrophobicity, random coil increased with oxidant concentration, whereas the total sulfhydryl and α-helix content decreased in both oxidizing systems. The turbidity and particle size were increased after oxidant treatment, indicating oxidation promoted the cross-linking and aggregation of protein, and the degree of aggregation was higher in hemin treated MP compared with that incubated with FeCl3. The biochemical changes of MP resulted in an uneven and loose gel network structure, which significantly reduced the gel strength and water holding capacity (WHC) of the gel.

Trajectories of oxygen saturation within 6-72 hours after birth in neonates at moderate altitude: a prospective longitudinal cohort study.

BACKGROUND: Trajectories of pulse oxygen saturation (SpO2) within the first few days after birth are important to inform the strategy for identifying asymptomatic hypoxemic disease but remain poorly substantiated at higher altitudes. METHODS: We performed a longitudinal cohort study with consecutive neonates at a local hospital in Luchun County, China, at an altitude of 1650 m between January and July 2020. We repeatedly measured the pre- and post-ductal SpO2 values at 6, 12, 18, 24, 36, 48, and 72 hours after birth for neonates without oxygen supplements. All neonates underwent echocardiography and were followed up to 42 days after discharge. We included neonates without hypoxemic diseases to characterize the trajectories of SpO2 over time using a linear mixed model. We considered the 2.5th percentile as the reference value to define hypoxemic conditions. RESULTS: A total of 1061 neonates were enrolled. Twenty-five had non-cardiac hypoxemic diseases, with 84% (21/25) presenting with abnormal SpO2 within 24 hours. One had tetralogy of Fallot identified by echocardiography. Among the 1035 asymptomatic neonates, SpO2 values declined from 6 hours after birth, reached a nadir at 48 hours, and tended to level off thereafter, with identical patterns for both pre- and post-ductal SpO2. The reference percentile was 92% for both pre- and post-ductal SpO2 and was time independent. CONCLUSIONS: A decline within 48 hours features SpO2 trajectories within the first 72 hours at moderate altitude. Our findings suggest that earlier screening may favorably achieve a benefit-risk balance in identifying asymptomatic hypoxemic diseases in this population.

Hourly personal temperature exposure and heart rate variability: A multi-center panel study in populations at intermediate to high-risk of cardiovascular disease.

BACKGROUND: Several studies reported temperature exposure was associated with altered cardiac automatic function, while this effect of temperature on hourly heart rate variability (HRV) among populations with cardiovascular risks was seldom addressed. METHODS: We conducted this panel study in four Chinese cities with three repeated visits among 296 participants at intermediate to high-risk of cardiovascular disease (CVD). Real-time temperature level and 24-h ambulatory electrocardiogram were monitored during each seasonal visit. Linear mixed-effects models were used to investigate associations between individual temperature and HRV parameters, and the seasonal effects and circadian effect were also evaluated. RESULTS: We found the overall downward trend of hourly HRV associated with acute exposure to higher temperature. For each 1 °C increment in temperature of 1-3 h prior to HRV measurements (lag 1-3 h), hourly standard deviation of normal-to-normal intervals (SDNN) decreased by 0.38% (95% confidence interval [CI]: 0.22, 0.54), 0.28% (95% CI: 0.12, 0.44), and 0.20% (95% CI: 0.04, 0.36), respectively. Similar inverse associations between temperature and HRV were observed in stratified analyses by temperature level. Inverse associations for cold and warm seasons were also observed, despite some effects gradually decreased and reversed in the warm season as lag times extended. Moreover, HRV showed a more significant reduction with increased temperature during daytime than nighttime. Percent change of hourly SDNN was -0.41% (95% CI: -0.62, -0.21) with 1 °C increment of lag 1 h during daytime, while few obvious changes were revealed during nighttime. CONCLUSIONS: Generally, increasing temperature was significantly associated with reduced HRV. Inverse relationships for cold and warm seasons were also observed. Associations during daytime were much more prominent than nighttime. Our findings clarified the relationship of temperature with HRV and provided evidence for prevention approaches to alleviate cardiac automatic dysfunction among populations at intermediate to high-risk of CVD.