Clinical characteristics and outcomes of acute liver failure in neonates: a retrospective cohort in China.

Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28 days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48 days; 26 days for hypoxic/ischemic injury and 43 days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018).   Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.

Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening.

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.

Elevated first-trimester hepcidin level is associated with reduced risk of iron deficiency anemia in late pregnancy: a prospective cohort study.

Background: Iron deficiency (ID) and iron deficiency anemia (IDA) during pregnancy are highly prevalent worldwide. Hepcidin is considered an important biomarker of iron status. Currently, few longitudinal cohort studies have assessed the potential causal relationship between hepcidin and ID/IDA. Therefore, we aimed to investigate the association of first-trimester maternal serum hepcidin with third-trimester ID/IDA risk in a prospective cohort. Methods: Total of 353 non-ID/IDA pregnant women at 11-13 weeks' gestation were enrolled in Southern China and followed up to 38 weeks of gestation. Data on demography and anthropometry were obtained from a structured questionnaire at enrollment. Iron biomarkers including hepcidin were measured at enrollment and follow-up. Regression models were used to evaluate the association of first-trimester hepcidin with third-trimester ID/IDA risk. Results: Serum hepcidin levels substantially decreased from 19.39 ng/mL in the first trimester to 1.32 ng/mL in the third trimester. Incidences of third-trimester ID and IDA were 46.2 and 11.4%, respectively. Moreover, moderate and high levels of first-trimester hepcidin were positively related to third-trimester hepcidin (log-transformed ß = 0.51; 95% CI = 0.01, 1.00 and log-transformed ß = 0.66; 95% CI = 0.15, 1.17). Importantly, elevated first-trimester hepcidin was significantly associated with reduced risk of third-trimester IDA (OR = 0.38; 95% CI = 0.15, 0.99), but not with ID after adjustment with potential confounders. Conclusion: First-trimester hepcidin was negatively associated with IDA risk in late pregnancy, indicating higher first-trimester hepcidin level may predict reduced risk for developing IDA. Nonetheless, given the limited sample size, larger studies are still needed.

Secular trends of birth weight and its associations with obesity and hypertension among Southern Chinese children and adolescents.

OBJECTIVES: The association of low or high birth weight (L/HBW) with obesity and hypertension in childhood remains unclear. We aimed to identify the secular trend of birth weight distribution and its relationship to obesity and hypertension in Southern Chinese children and adolescents. METHODS: 6,561 individuals (6-17-year-old) were enrolled by multistage cluster sampling to observed the trend of birth weight distribution and its associated factors. 1,218 were further selected by group matching to investigate the correlation between birth weight and obesity or hypertension. RESULTS: Between 1997 and 2008, a significant decline in the LBW rate and no significant change in the HBW rate was found. LBW was associated with maternal BMI<18 kg/m2 (OR1.79, 95% CI 1.08-2.97) during pregnancy, while maternal BMI between 25.0 and 27.9 kg/m2 (OR1.62, 95% CI 1.04-2.52) and paternal BMI>28 kg/m2 (OR1.64, 95% CI 1.02-2.63) during pregnancy were associated with HBW. The prevalence of obesity was significantly higher with HBW than normal birth weight (NBW) or LBW (16.73, 6.25 and 5.50%, respectively). The prevalence rates of suspected hypertension were 1.62, 1.25 and 1.49% among LBW, NBW and HBW, respectively (p>0.05). LBW decreased the risks of childhood overweight (OR0.31, 95% CI 0.18-0.54), but had no effect on suspected hypertension. HBW increased the risks of childhood obesity (OR2.19, 95% CI 1.50-3.20), but decreased the risks of suspected hypertension (OR0.22, 95% CI 0.09-0.58). CONCLUSIONS: HBW was positively associated with childhood obesity, and parental BMIs management might be one of the measurements to control birth weight to lessen childhood obesity.

Galloway-Mowat Syndrome Type 3 Caused by OSGEP Gene Variants: A Case Report and Literature Review.

Background: Galloway-Mowat syndrome type 3 (GAMOS3) is an extremely rare and severe autosomal-recessive disease characterized by early-onset nephrotic syndrome (NS), microcephaly and neurological impairment. Reported GAMOS cases have gradually increased since pathogenic OSGEP variants were identified as the aetiology in 2017. Methods: Using whole-exome sequencing and a data analysis process established by Children's Hospital of Fudan University, the clinical and molecular features of 3 infants with OSGEP mutations were summarized. Literature regarding the clinical features of GAMOS3 caused by OSGEP variants was reviewed. Results: Thirty-seven individuals (3 from this study) from 34 families were included. Twenty-two different OSGEP variants were identified. The c.740G>A (p.Arg247Gln) variant in OSGEP was detected in 15 families (44%), all from Asia. Most affected individuals (including patients I and II in this study) showed a typical phenotype, including microcephaly (92%) with brain anomalies (97%), developmental delay (81%), congenital NS (54%), and craniofacial (94%) and skeletal dysmorphism (84%). Renal manifestations varied from proteinuria (94%, median onset = 1.5 months) to NS (83%) and end-stage renal disease (48%, 11 months) during follow-up. Patients with congenital NS had a lower survival probability (median survival time = 3 months) than those without congenital NS (78 months) (P < 0.01, log-rank test). Conclusion: GAMOS3 is a progressive renal-neurological syndrome with a poor prognosis, especially with congenital NS. Microcephaly with dysmorphic features are vital clues to further evaluate renal impairment and brain anomalies. Timely molecular diagnosis is crucial for clinical decision-making, appropriate treatment and genetic counselling.

Iron Supplementation Is Associated with Improvement of Motor Development, Hemoglobin Level, and Weight in Preterm Infants during the First Year of Life in China.

Iron supplementation is recommended for preterm infants due to impaired iron endowment. However, the health outcomes of this recommendation remain controversial. Thus, this study aimed to determine the association of iron supplementation with neurobehavioral development, hemoglobin (Hb), and anthropometric characteristics in preterm infants. A retrospective cohort design was applied to collect data from 1568 preterm infants at 0-3 months of corrected age (mo CA) from a hospital in South China. Infants were categorized into a 3-month iron supplementation group (IG, n = 697) or a control group (CG, n = 871) according to medical records, and then followed through to 12 mo CA. Data on neurobehavioral development, anthropometry, Hb level, history of diseases, and nutrition were collected at 3, 6, and 12 mo CA. The results showed that, compared with the CG, iron supplementation was positively related to improved gross motor skills and weight at 6 mo CA (ß = 1.894, ß = 5.322) and 12 mo CA (ß = 4.019, ß = 6.830) and fine motor skills at 12 mo CA (ß = 1.980), after adjustment for confounding factors including illness, nutritional supplements, and diet. Iron supplementation was also related to elevated Hb levels and its increase at 3 mo CA (ß = 2.196, ß = 3.920) and 6 mo CA (ß = 3.011, ß = 7.259). In conclusion, iron supplementation for 3 months in Chinese preterm infants is positively associated with improved motor development, elevated Hb levels, and higher body weight during the first year of life.

Soy Food Intake Associated with Obesity and Hypertension in Children and Adolescents in Guangzhou, Southern China.

The associations between soy food intake and cardio-metabolic risk factors in children remain unclear due to limited evidence. We aim to explore soy food intake and its association with the risks of obesity and hypertension in Chinese children and adolescents. A total of 10,536 children and adolescents aged 7-18 years (5125 boys and 5411 girls) were enrolled in a cross-sectional study in Guangzhou City, southern China. Data on demographic characteristics and dietary consumption were collected using self-reported questionnaires, and anthropometric characteristics were measured. Obesity, abdominal obesity, and hypertension were defined using Chinese criteria for children and adolescents. A multiple logistic regression model was applied to estimate the association between soy food intake and obesity and hypertension. Roughly 39.5% of the participants consumed soy food more than three times per week. The mean amounts of liquid and solid soy food intake were 0.35 ± 0.54 cups/day and 0.46 ± 0.63 servings/day, respectively. The adjusted odds ratios (OR) of hypertension among those with high liquid soy food intake and a high frequency of all soy food intake (more than three times/week) were 0.79 (95% confidence interval (CI), 0.67-0.94), and 0.83 (95% CI, 0.70-0.97) compared to those with no intake. Additionally, the adjusted OR of obesity among those with high solid soy food intake and a high frequency of all soy food intake were 1.34 (95% CI, 1.09-1.63) and 1.30 (95% CI, 1.07-1.58), respectively. In conclusion, 39.5% of southern Chinese children and adolescents had high soy food intake (more than three times/week), which was significantly associated with a lower prevalence of hypertension and a greater prevalence of obesity.

Antenatal Iron-Rich Food Intervention Prevents Iron-Deficiency Anemia but Does Not Affect Serum Hepcidin in Pregnant Women.

BACKGROUND: Limited evidence supports the efficacy of iron-rich foods (IRFs) in improving iron status during pregnancy. OBJECTIVES: The study aims to evaluate the effect of IRFs on iron status and biomarkers of iron metabolism in the third trimester of pregnancy. METHODS: A total of 240 pregnant women at 11-13 wk of gestation without iron-deficiency anemia (IDA) in South China were recruited to this single-blind clinical trial [non-IDA referred to both hemoglobin (Hb) ≥110g/L and serum ferritin (SF) ≥15ng/mL],  randomly assigned to 1) control, 2) IRFs containing 20 mg iron/d (IRF-20), or 3) IRFs containing 40 mg iron/d (IRF-40). The IRFs were consumed 3 days a week, including pork liver, chicken/duck blood, soybean, and agaric. The IRFs started at recruitment and ended in the predelivery room. Primary outcome included anemia (Hb <110 g/L), iron deficiency (ID, definition 1: SF <15 ng/mL; definition 2: SF <12 ng/mL), and IDA (ID and Hb <110 g/L). Secondary outcome was plasma Hb and iron indices, including SF, serum hepcidin, and iron. RESULTS: All participants who completed the trial with full data (n = 170) were included in the analysis. At the endline, both intervention groups showed lower ID and IDA rates than control. Specifically, IRF-40 showed a lower ID (SF <12 ng/mL) rate than control (9.0% compared with 22.8%, P = 0.022). For IDA by definition 1, the incidence in IRF-40 was lower than that in control (1.9% compared with 8.9%, P = 0.045). For IDA by definition 2, the incidence in IRF-20 was lower than that in control (3.9% compared with 17.9%, P = 0.049). Moreover, IRF-20 showed higher SF concentrations than control (P = 0.039). No effects of IRFs on anemia (P = 0.856), plasma Hb (P = 0.697), serum hepcidin (P = 0.311), and iron (P = 0.253) concentrations were observed. The assessed iron intakes were 22.2 mg/d in IRF-20 and 25.0 mg/d in IRF-40, respectively. CONCLUSIONS: Antenatal IRFs reduce the risk of ID and IDA in late pregnancy, although the present results are inadequate to confirm an ideal dosage (No. ChiCTR1800017574).

Case Report: Clinical Features of Congenital Portosystemic Shunts in the Neonatal Period.

Objective: The aim of this single-center retrospective study was to analyze the clinical characteristics, treatment options, and course of neonatal-onset congenital portosystemic shunts (CPSS). Methods: We included all patients with CPSS who presented with clinical symptoms within the neonatal period in our institution between 2015 and 2020. Results: Sixteen patients were identified, including 13 patients with intrahepatic portosystemic shunts (IPSS) and three patients with extrahepatic portosystemic shunts (EPSS). The median age of diagnosis was 16 days (range prenatal 24 weeks-12 months). Hyperammonemia (60%), neonatal cholestasis (44%), elevated liver enzyme (40%), hypoglycemia (40%), thrombocytopenia (38%), and coagulation abnormalities (23%) appeared in neonatal CPSS. Twelve patients (75%) presented with congenital anomalies, of which congenital heart disease (CHD) (44%) was the most common. Thirteen patients with IPSS initially underwent conservative treatment, but two of them were recommended for the catheter interventional therapy and liver transplantation, respectively, due to progressive deterioration of liver function. Spontaneous closure occurred in nine patients with IPSS. The shunt was closed using transcatheter embolization in one patient with EPSS type II. Another patient with EPSS type II underwent surgical treatment of CHD firstly. The remaining patient with EPSS type Ib received medical therapy and refused liver transplantation. Conclusion: Hyperammonemia, neonatal cholestasis, elevated liver enzyme, hypoglycemia, and thrombocytopenia are the main complications of neonatal CPSS. Moreover, CPSS is associated with multiple congenital abnormalities, especially CHD. Intrahepatic portosystemic shunts may close spontaneously, and conservative treatment can be taken first. Extrahepatic portosystemic shunts should be closed to prevent complications.

Effects of Caloric Restriction and Rope-Skipping Exercise on Cardiometabolic Health: A Pilot Randomized Controlled Trial in Young Adults.

The aim of this study is to investigate the effects of calorie restriction (CR), rope-skipping (RS) exercise, and their joint effects on cardiometabolic health in young adults. An 8-week randomized trial was conducted on 46 undergraduates aged 19-21 y from South China. The participants were randomized into the following three groups: Calorie restriction (CR) group (n = 14), Rope-skipping (RS) group (n = 14), and CR plus RS (CR-RS) group (n = 12). At both allocation and the end of the intervention, data on anthropometry, serum metabolic, and inflammatory markers were collected. A total of 40 participants completed the intervention and were included in the analysis. After the 8-week intervention, the participants from the CR group and the CR-RS group reduced in body weight (-1.1 ± 1.7 kg, -1.3 ± 2.0 kg), body mass index (-0.4 ± 0.6 kg/m2, -0.5 ± 0.7 kg/m2), body fat percentage (-1.2 ± 1.6%, -1.7 ± 1.8%), and body fat mass (-1.1 kg (-2.2, -0.3), -1.1 kg (-2.5, -0.4)) compared to the baseline (p < 0.05 or p = 0.051). For metabolic and inflammatory factors, the participants in the CR-RS group showed significant decreases in low density lipoprotein cholesterol (-0.40 mmol/L) and interleukin-8 (-0.73 mmol/L). While all the above markers showed no significant difference among the groups after intervention, in the subgroup of overweight/obese participants (n = 23), the CR-RS group had significantly lower blood pressure, fasting insulin, homeostatic model assessment of insulin resistance, tumor necrosis factor-α, and interleukin-8 levels than the CR or RS groups (p < 0.05). In conclusion, both CR and CR-RS could reduce weight and improve body composition in young adults. More importantly, in those with overweight or obesity, CR-RS intervention might be superior to either CR or RS in improving cardiometabolic health.

Non-invasive cardiac output measurement by electrical cardiometry and M-mode echocardiography in the neonate: a prospective observational study of 136 neonatal infants.

BACKGROUND: Electrical cardiometry (EC) is a continuous, non-invasive method for measuring cardiac output (CO). This study investigates the correlation and consistency of CO values in newborns obtained by using EC and M-mode echocardiography (Teichholz formula). METHODS: In this prospective observational study, simultaneous measurement of CO was implemented with EC (COec) and M-mode echocardiography (COm) in neonates. The absolute values of CO measured by the two methods were converted to Z-scores. Following that, Pears's correlation analyses and the Bland-Altman index were employed to analyze the correlation and consistency of COec Z-scores and COm Z-scores. RESULTS: A total of 136 neonates (93 preterm infants) were enrolled in this study, and EC and M-mode echocardiography comparative studies were conducted 155 times. The mean value of COec and COm demonstrated significant statistical differences (P<0.001). A moderate correlation (r=0.601; P<0.001) was found between the two methods. The Bland-Altman index value was 3.2%, which remained less than 5% in the low birth weight (LBW) (2.1%), non-LBW (3.4%), spontaneous respiration (3.1%), nasal continuous positive airway pressure (nCPAP) (4.0%), mechanical ventilation (2.9%), hemodynamic significance of the patent ductus arteriosus (hsPDA) (4.3%), and non-hsPDA (3.7%) groups, respectively. CONCLUSIONS: Although the absolute values of CO measured by EC and M-mode echocardiography were not interchangeable, the distribution of CO in EC and M-mode echocardiography was similar.

Single-course antenatal corticosteroids is related to faster growth in very-low-birth-weight infant.

BACKGROUND: Antenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants. METHODS: A multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23-37 weeks' gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA < 28 weeks, 28 weeks ≤ GA < 32 weeks and 32 weeks ≤ GA < 37 weeks. Multiple linear regression and multilevel model were applied to analyze the association of ACS with feeding and growth outcomes. RESULTS: A total of 841 infants were recruited. The results, just in very-low-birth-weight preterm infants born at 28-32 weeks' gestation, showed both single and repeated course of ACS regimens had shorter intubated ventilation time compared to non-ACS regimen. Single-course ACS promoted the earlier application of amino acid and enteral nutrition, and higher rate of weight increase (15.71; 95%CI 5.54-25.88) than non-ACS after adjusting for potential confounding factors. No associations of repeated course ACS with feeding, mean weight and weight increase rate were observed. CONCLUSIONS: Single-course ACS was positively related to feeding and growth outcomes in very-low-birth-weight preterm infants born at 28-32 weeks' gestation. However, the similar phenomenon was not observed in the repeated course of ACS regimen.

Effects of tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) on sex-dependent alterations of thyroid hormones in adult zebrafish.

Organophosphate flame retardants (OPFRs) have been widely used as alternatives to polybrominated diphenyl ethers for fire prevention. OPFRs are suspected of causing potential thyroid disruption in humans. In fish, their thyroid hormone modulation is reported but the mechanisms of this modulation are less understood. Thyroid-disturbing effects of OPFRs were evaluated using adult zebrafish (Danio rerio) following 14d exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) or triphenyl phosphate (TPP). Plasma concentrations of thyroid hormones were measured and transcriptions of several genes involved in thyroid function were quantified in brain, thyroid, and liver. Exposure to TDCPP or TPP led to significant decreases in plasma triiodothyronine (T3) and thyroxine (T4) concentrations in the male fish, while the increases were observed in the female fish. Exposure to the OPFRs also altered the transcription of regulatory genes and receptors in hypothalamus, pituitary, and thyroid of the fish in sex-dependent manner. In the male fish, transcriptions of corticotropin-releasing hormone (crh) and thyroid-stimulating hormone (tsh) in the brain were significantly up-regulated, probably as a compensation for hypothyroidism, but thyroglobulin (tg) and deiodinase 2 (dio2) were down-regulated in thyroid or liver. In contrast, in the females, transcriptions of crh and tsh genes were significantly down-regulated. These observations show that TDCPP and TPP exposure can lead to sex-dependent disruptions of thyroid hormone balances in the adult zebrafish through alterations of the hypothalamus-pituitary-thyroid (HPT) axis.

[The Determination of Tungsten Extracted from Prefi llable Syringes by ICP-MS].

First, simply expounded the purpose and meaning of detecting tungsten extracted from prefi lable syringes: And then, designed simulation experiment for extracting tungsten from prefi lable glass syringes. and established determination methods of tungsten content by ICP-MSL Finaly, evaluated the limit of content of tungsten ?extracting from simulation experiment.

3-[(E)-1-(Benzyl-oxyimino)eth-yl]-2-oxo-2H-chromen-7-yl acetate.

The title compound, C(20)H(17)NO(5), was prepared by the reaction of 3-acetyl-2-oxo-2H-chromen-7-yl acetate with benzyl-oxy-amine. The mol-ecule adopts an E configuration with respect to the C=N double bond. The dihedral angles between the coumarin ring system, the phenyl ring and the C=N-O-C plane of the oxime unit are 35.83 (6), 35.8 (2) and 69.99 (15)°, respectively. In the crystal, a two-dimensional supra-molecular network is assembled through weak inter-molecular C-H⋯O hydrogen-bonding inter-actions.