Prediction of cord blood leptin on infant's neurodevelopment: A birth cohort in rural Yunnan, China.

BACKGROUND: Leptin, one of the peptide hormones secreted by adipocytes, plays a vital part in metabolism, but its role in early-life neurodevelopment remains poorly understood. METHODS: We performed leptin analysis on 323 cord blood samples collected from a birth cohort in Yunnan rural area, China, and assessed infants' neurodevelopment at one year of age by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Multiple linear regression and binary logistic regression models were used to explore the associations between cord blood leptin (CBL) concentrations and infants' neurodevelopment and the ability of CBL to predict the probabilities of infants' neurodevelopment delay. RESULTS: Overall, 323 infants were included in this study. The median concentration of CBL was 4.7 ng/ml. The proportion of 1-year-old infants identified as being neurodevelopmental delayed was 34.5%, and delays in cognitive, language, and motor domains were 11.1%, 26.6%, and 13.9%, respectively. Multiple linear regression analyses manifested that the CBL concentration (log10-transformed) was positively correlated with the cognitive, language, and motor composite scores in infants, respectively (ß = 7.76, 95%CI: 3.81-11.71; ß = 6.73, 95%CI: 3.41-10.06; and ß = 6.88, 95%CI: 3.48-10.29, respectively). Binary logistic regression analysis showed that compared with the higher, lower CBL (< 4.7 ng/ml) yielded a 1.41-fold increase in the risk of language development delay (OR = 2.41，95%CI: 1.42-4.09), a 1.49-fold higher risk of motor development delay (OR = 2.49, 95%CI: 1.25-4.96), and a 1.71-fold higher risk of neurodevelopment delay (OR = 2.71, 95%CI: 1.64-4.48) among infants. The prediction models showed that the probabilities of development delay in infants' language, motor, and neurodevelopment increased with the decline of CBL concentrations [rs = -0.63 (95% CI: -0.71, -0.56), rs = -0.46 (95% CI: -0.55, -0.38), rs = -0.55 (95% CI: -0.63, -0.46), respectively]. CONCLUSION: The decline of CBL was associated with the decrease in infants' neurodevelopment scores at one year of age. CBL below 4.7 ng/ml may increase the risk of infants' neurodevelopment delay. The probabilities of infants' neurodevelopment delay increased with the decrease of CBL concentrations. CBL may be a predictor of the probability of children's neurodevelopment delay.

Impact of maternal age on neonatal outcomes among very preterm infants admitted to Chinese neonatal intensive care units: a multi-center cohort study.

Background: The percentage of advanced maternal age (aged over 35 years) mothers has been rising across the world, the evidence of maternal age on neonatal outcomes from low- and middle-income countries is scarce. Our objective was to evaluate the effect of maternal age on mortality and major morbidity among very preterm infants admitted to Chinese neonatal intensive care units. Methods: Data from a retrospective multi-center cohort of all complete care very preterm infants admitted to 57 neonatal intensive care units that participated in the Chinese Neonatal Network from January 1st to December 31st, 2019 were analyzed. Neonatal outcomes including mortality or any major morbidity, defined as necrotizing enterocolitis stage 2 or 3, moderate & severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. A multiple logistic regression model was constructed to analyze the independent association between maternal age and neonatal outcome. Results: Among 7,698 eligible newborns, 80.5% of very preterm infants were born to mothers between the ages of 21 and 35 years, with 18.0% born to mothers >35 years and 1.5% born to mothers <21 years. Higher rates of maternal hypertension, maternal diabetes, cesarean deliveries, antenatal steroid usage were noted as maternal age increased. The proportion of prenatal care, cesarean section, antenatal steroid usage and inborn for very preterm infants born to mothers <21 years was lower than those of mothers of other ages. Compared to the ages of 21-35 years group, the odds of severe intraventricular hemorrhage (adjusted odd ratio: 2.00, 95% CI: 1.08-3.71) was significantly higher in the ages of 15-20 years group. Increasing maternal age was associated with higher rates of small for gestational age and lower birth weight of very preterm infants, but no correlation between advanced maternal age and very preterm infants mortality or major morbidity. Conclusions: Among very preterm infants, increasing maternal age was associated with higher rates of small for gestational age but not neonatal mortality or major morbidity. Young maternal age may increase the risk of severe intraventricular hemorrhage of very preterm infants.

Effects of prenatal and infant daily exposure to pyrethroid pesticides on the language development of 2-year-old toddlers: A prospective cohort study in rural Yunnan, China.

BACKGROUND: Prenatal and infant daily exposures to pyrethroid pesticides (PYRs), used in the elimination of harmful organisms in the family environment and agricultural activities, may have an impact on children's language development. OBJECTIVES: To determine the impacts of prenatal and infant PYRs exposure on 2-year-old toddlers' language development. METHODS: From January 2016 to December 2018, women in the third trimester of pregnancy, in Yunnan rural area, China, were recruited, and the development of their newborns was observed from birth till the age of two. We examined three PYRs metabolites: 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-2,2dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) in urine samples collected from women in the third trimester of pregnancy and their infants of 6-8 months after birth, and assessed language development of 2-year-old toddlers by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Generalized linear models were used to analyze the impacts of exposure to PYRs on 2-year-old toddlers' language development. RESULTS: The median concentrations of 3PBA, 4F3PBA and DBCA creatinine-adjusted were 0.21, 0.19, and 0.15 µg/g in pregnancy, and 0.25, 0.72, and

Effects of prenatal exposure to pyrethroid pesticides on neurodevelopment of 1-year- old children: A birth cohort study in China.

Pregnant women have been ubiquitously exposed to pyrethroid pesticides. Previous studies, mainly based on third trimester measurements of maternal urinary pyrethroid metabolites, have reported inconsistent findings in the effects of prenatal pyrethroid exposure on children's neurodevelopmental outcomes. The purpose of this study was to clarify if pyrethroid exposure during the entire three trimesters of pregnancy may be associated with deleterious effects on infant neurodevelopmental status, particularly at a high dosage of exposure. We measured maternal urinary concentrations of pyrethroid metabolites in all trimesters of pregnancy and assessed children's neurodevelopment at one year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multiple linear regression models were used to estimate the effects of metabolites (3-PBA, 4 F-3-PBA, cis-DBCA) in each trimester on BSID-III composite scores. Logistic regression analyses were applied to predict developmental delay vs non-delayed status (cut-off composite score of below 80 for developmental delay) based on the maternal levels of pyrethroid metabolites. In the first, second and third trimesters of pregnancy, the detection rates of pyrethroid metabolites were 94.7%, 90.7%, and 89.0%; the 50th percentiles of exposure level were 0.24 µg/g, 0.24 µg/g and 0.21 µg/g for 3-PBA, 0.14 µg/g, 0.17 µg/g and 0.15 µg/g for 4 F-3PBA, 0.21 µg/g, 0.25 µg/g and 0.19 µg/g for cis-DBCA respectively. In the second trimester, 3-PBA was inversely associated with Cognition and Language scores [ß = -3.34 (95% CI = -6.11, -0.57) and ß = -2.90 (95% CI = -5.20, -0.61), respectively], and significantly increased the risk of Cognition and Language developmental delay [OR= 1.64 (95% CI = 1.03, 2.62) and OR = 1.52 (95% CI = 1.06, 2.19), respectively]; cis-DBCA was inversely associated with Adaptive Behavior scores [ß = -0.73 (95% CI = -1.27, -0.19)], and significantly increased the risk of Adaptive Behavior developmental delay [OR= 1.11 (95% CI = 1.02, 1.21)]. When the maternal levels of pyrethroid metabolites were stratified into the regression models according to the 90th percentile of exposure, in the first trimester, Cognition and Motor scores were inversely associated with higher cis-DBCA [ß = -7.19 (95% CI = -12.97, -1.41) and ß = -8.20 (95% CI = -13.35, -3.05), respectively], Language scores were inversely associated with higher 3-PBA [ß = -6.01 (95% CI = -10.96, -1.06)]; in the second trimester, Cognition scores were inversely associated with higher cis-DBCA [ß = -6.64 (95% CI = -12.51, -0.76)], Language scores were inversely associated with higher 3-PBA [ß = -5.17 (95% CI = -10.07, -0.27)] and cis-DBCA [ß = -5.40 (95% CI = -10.28, -0.52)]. We concluded that pyrethroid exposure in the first and second trimesters was associated with poorer infants neurodevelopmental outcomes at one year of age, and these effects were particularly pronounced at high levels of pyrethroid exposure.

Long Non-coding RNA TUG1 Modulates Expression of Elastin to Relieve Bronchopulmonary Dysplasia via Sponging miR-29a-3p.

Objective: Multiple studies have highlighted that long non-coding RNAs (lncRNAs) may exert paramount roles in relieving bronchopulmonary dysplasia (BPD). The aim of our investigation is to probe the role and mechanism of lncRNA taurine upregulated gene 1 (TUG1) in BPD. Methods: The current mouse model of BPD was simulated by induction of hyperoxia, and hyperoxia-induced mouse type II alveolar epithelial (MLE-12) (MLE-12) cells were established as a cellular model. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine relative expressions of TUG1, miR-29a-3p, and elastin (ELN). We assessed cell apoptosis by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. Western blot was used for detection of apoptosis-related proteins. Moreover, cell viability was tested by cell counting kit-8 (CCK-8) assay. Inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter (DLR) assay was employed to confirm relationship between genes. Results: Upregulation of miR-29a-3p was found in lung tissues of BPD mice compared with lung tissues without BPD, while downregulations of TUG1 and ELN were discovered in BPD tissues in comparison with tissues without BPD. Increasing TUG1 was shown to alleviate lung injury of BPD mice and promote proliferation of hyperoxia-induced MLE-12 cells. Meanwhile, TUG1 inhibited inflammatory response and cell apoptosis in lung tissues of BPD mice and hyperoxia-induced MLE-12 cells. miR-29a-3p was targeted by TUG1 and negatively modulated by TUG1. ELN was inversely regulated by miR-29a-3p. Meantime, suppressive effects of TUG1 on apoptosis and inflammation were reversed by decreasing ELN or increasing miR-29a-3p in hyperoxia-induced MLE-12 cells. Conclusion: lncRNA TUG1 relieved BPD through regulating the miR-29a-3p/ELN axis, which provided a therapeutic option to prevent or ameliorate BPD.

[Clinical application of whole exome sequencing in monogenic hereditary disorders in critically ill newborns].

OBJECTIVE: To explore the value and significance of the clinical application of whole exome sequencing (WES) in monogenic hereditary disorders in critically ill newborns. METHODS: The critically ill newborns in the neonatal intensive care unit with suspected hereditary diseases or unclear clinical diagnosis from June 2016 to December 2018 were enrolled. The whole blood samples from both newborns and parents were collected for WES. The detected genetic mutations were classified, the mutations associated with clinical phenotypes were searched for, and Sanger sequencing was performed to verify the mutations. RESULTS: A total of 45 newborns were enrolled, including 22 males and 23 females, and the median age of onset was 2.0 days. Of the 45 newborns, 12 (27%) were confirmed with monogenic hereditary disorders by molecular diagnostics, and the median age at diagnosis was 31.5 days. Of the 12 newborns with monogenic hereditary disorders, 5 (42%) were partially associated with clinical phenotypes but confirmed with monogenic hereditary disorders by additional information supplement and analysis. The improvement rate of newborns with monogenic hereditary disorders was 67% (8/12) after treatment. CONCLUSIONS: WES technology is a powerful tool for finding genetic mutations in monogenic hereditary disorders in critically ill newborns and can play a crucial role in clinical decision-making. However, a comprehensive interpretation of sequence data requires physicians to take the clinical phenotypes and the results of WES into consideration simultaneously.

[Levels of blood free carnitine in preterm infants with different gestational ages and birth weights].

OBJECTIVE: To examine blood concentrations of free carnitine (FC) in preterm infants with different gestational ages (GA) and birth weights (BW). METHODS: A total of 3 368 preterm infants were enrolled as subjects. According to GA, they were divided into extremely preterm birth (EPTB) group (GA <28 weeks; n=39), very preterm birth (VPTB) group (28 ≤GA <32 weeks; n=405), moderately preterm birth (MPTB) group (32 ≤GA <34 weeks; n=507), and late preterm birth (LPTB) group (34 ≤GA <37 weeks; n=2 417); according to BW, they were divided into extremely low birth weight (ELBW) group (BW <1 000 g; n=36), very low birth weight (VLBW) group (1 000 g ≤BW <1 500 g; n=387), low birth weight (LBW) group (1 500 g ≤BW <2 500 g; n=1 873), and normal birth weight (NBW) group (2 500 g ≤ BW <4 000 g; n=1 072). Blood concentrations of FC were measured between 72 hours and 7 days after birth. RESULTS: The EPTB and VPTB groups had significantly higher FC concentrations than the MPTB and LPTB groups (P<0.05), and the MPTB group had significantly higher FC concentrations than the LPTB group (P<0.05). The lower limit of the 95% medical reference range of FC increased with the reduction in GA. The ELBW and VLBW groups had significantly higher FC concentrations than the LBW and NBW groups (P<0.05). The LBW group had significantly higher FC concentrations than the NBW group (P<0.05). The lower limit of the 95% medical reference range of FC increased with the reduction in BW. CONCLUSIONS: There is a significant increase in blood FC concentrations in very/extremely preterm infants and very/extremely low birth weight infants, and tend to decrease with the increases in GA and BW.

[A clinical study of growth and metabolism of small for gestational age infants].

OBJECTIVE: To study the differences in growth and metabolism between small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants. METHODS: A total of 1 370 preterm infants were enrolled in this study. According to the association between gestational age and birth weight, they were divided into SGA group with 675 infants and AGA group with 695 infants. The two groups were compared in terms of general conditions, physical growth and blood biochemical parameters. RESULTS: The SGA group had a significantly longer length of hospital stay than the AGA group (P<0.05). Compared with the AGA group, the SGA group had significantly lower body weight, body weight Z score, and body length at discharge and significantly higher incidence rate of extrauterine growth retardation and growth rate of head circumference (P<0.05). Compared with the AGA group, the SGA group had significantly longer time to full enteral nutrition and duration of parenteral nutrition (P<0.05). Compared with the AGA group, the SGA group had significantly higher levels of albumin, prealbumin, and serum phosphorus on admission and total bile acid before discharge, as well as a significantly lower albumin level before discharge (P<0.05). The incidence rates of asphyxia, neonatal respiratory distress syndrome, myocardial damage, feeding intolerance, pneumonia, sepsis, hypoglycemia and hypothyroxinemia in the SGA group were significantly higher than in the AGA group (P<0.05). CONCLUSIONS: Compared with AGA infants, SGA infants have significantly delayed physical development during hospitalization and significantly higher incidence rates of extrauterine growth retardation and related complications.

[Effect of prone positioning on respiratory function in very preterm infants undergoing mechanical ventilation].

OBJECTIVE: To explore the effect of prone positioning on respiratory function in very preterm infants undergoing mechanical ventilation. METHODS: A total of 83 very preterm infants treated with mechanical ventilation were enrolled in the study and were randomly assigned to supine group and prone group. Four infants withdrew from the study and 79 infants completed treatment and observation (37 in the supine group and 42 in the prone group). Infants in both groups were mechanically ventilated in a volume assist-control mode. Infants in the prone group were ventilated in the supine position for 4 hours and in the prone position for 2 hours. Ventilator parameters, arterial blood gas analysis, and vital signs were recorded before grouping, every 6 hours in the supine group, and every hour after conversion into the prone position in the prone group, respectively. RESULTS: Fraction of inspired oxygen (FiO2), peak inspiratory pressure, mean inspiratory pressure, and duration of ventilation were significantly lower in the prone group than in the supine group (P<0.05); there were no significant differences in tidal volume or positive end-expiratory pressure between the two groups (P>0.05). The prone group had a significantly higher PO2/FiO2 ratio but significantly lower oxygenation index and respiratory rate than the supine group (P<0.05). There were no significant differences in arterial oxygen tension, pH, base excess, heart rate, or mean blood pressure between the two groups (P>0.05). CONCLUSIONS: Alternating ventilation between the prone position and supine position can improve oxygenation function, decrease the fraction of inspired oxygen, and shorten the duration of mechanical ventilation in very preterm infants undergoing mechanical ventilation.

[Epidemiological survey of childhood asthma in Kunming City, China].

OBJECTIVE: To investigate the prevalence of childhood asthma, and to find the distribution characteristics, precipitating factors, diagnosis and treatment status, and to provide scientific data for improving the prevention and management of asthma in children in Kunming City, China. METHODS: Children were selected by random cluster sampling. A standardized preliminary questionnaire was used for screening out possible patients in the survey. Diagnosis of asthma was confirmed by diagnostic criteria in suspected asthmatic children. Asthmatic children were further asked for past diagnosis and treatment with the questionnaire of asthma in children. RESULTS: The total asthma incidence rate was 1.40%. The prevalence of asthma in male and female children was 1.89% and 0.88% respectively (P<0.05). Children aged 0-5 years old had a higher prevalence of asthma (1.69%) than that of school-age children (6-14 years old, 1.21%). In all asthmatic children, 51.3% were previously diagnosed with classical asthma or cough variant asthma, 26.0% were suffered attacks from December to February, and 54.0% were suffered attacks at midnight or dawn. Respiratory tract infection (87.3%) was the most common triggers of asthma exacerbation. Antibiotics were used in 80.0%, bronchodilators in 66.0%, inhaled corticosteroid in 64.0%. A peak flow meter for monitoring lung function was used in 17% of asthmatic children over 5 years old. CONCLUSIONS: The prevalence of asthma is associated with age and gender in children aged 0-14 years old in Kunming City. Acute asthma attack occurs mostly in winter and at midnight or dawn. Respiratory tract infection is the most common trigger of asthma exacerbation. Nearly a half of patients with asthma had not been diagnosed with asthma in the early stage. Most asthmatic children use antibiotics and only two-thirds use bronchodilators or inhaled corticosteroid in the treatment. The treatment and management of asthma in children awaits improvement as well.

[Effects of triiodothyronine on the learning and memory behaviors in neonatal mice following excitotoxic brain damage].

OBJECTIVE: Some research has shown that learning and memory function impairments in rats with hypothyroidism are associated with triiodothyronine (T3) deficiency in neurons. This study aimed to investigate the effects of L-T3 administration on learning and memory behaviors in neonatal mice with excitotoxic brain damage. METHODS: Seventy-one 5-day-old ICR neonatal mice were randomly assigned to five groups: controls that received intracerebral and intraperitoneal injections of phosphate buffered saline (PBS) (n=14); a group that received intracerebral injections of ibotenic acid (IA) and intraperitoneal injection of PBS (n=14); 3 groups that received intracerebral injections of IA and intraperitoneal injection of L-T3 at 0.2, 0.5, and 1 microg/kg, respectively (n=14-15). Intraperitoneal injections were done 1, 24, 48, 72 and 96 hrs after intracerebral injections. Learning and memory functions were evaluated by the Y-maze discrimination learning test on postnatal days 33-34. RESULTS: The learning and memory functions in the highest L-T3 dose group were significantly better than those in the IA, and the lower L-T3 dose groups, presenting with decreased number of trials to criterion[15.8 + or - 4.5 vs 21.3 + or - 6.3 (IA group), 20.5 + or - 6.0 (0.2 microg/kg L-T3 group) or 21.0 + or - 6.5 (0.5 microg/kg L-T3 group); P<0.05], and achieving a higher correct percentage [91.4+ or - 9.5% vs 79.3 + or - 10.0% (IA group), 77.9 + or - 14.2% (0.2 microg/kg L-T3 group) or 80.7 + or - 12.2% (0.5 microg/kg L-T3 group); P<0.05]. CONCLUSIONS: High-dose L-T3 (1 microg/kg) may improve learning and memory functions in mice following excitotoxic brain damage.

[Neurobehavioral function of neonatal mice following excitotoxic brain damage].

OBJECTIVE: To assess the changes of neurobehavioral function in a neonatal mouse model of excitotoxic brain damage. METHODS: Fifty-five 5-day-old ICR neonatal mice were randomly assigned to three groups: blank (no intravenous) control (n=20), saline control (n=20) and excitotoxic brain damage model (ibotenic acid treatment, n=15). Behavioral function was evaluated by the surface righting reflex test (postnatal days 6-10), the swimming test (postnatal days 8-12) and the Y-maze discrimination learning test (postnatal days 33-34). RESULTS: Righting time in the surface righting reflex test in the ibotenic acid treatment group on postnatal days 6-10 was more prolonged than that in the two control groups (p<0.05). Swimming test scores in the ibotenic acid treatment group were significantly lower than those in the two control groups (p<0.05). In the Y-maze discrimination learning test, the mice from the ibotenic acid treatment group performed significantly worse than two control groups, presenting with increased learning times (19.79+/-2.42 vs 16.29+/-2.48 or 16.30+/-2.37; p<0.05) and achieving a lower correct percentage (86.7% vs 96.5% or 95.0%) (p<0.05). CONCLUSIONS: The developmental reflexes and learning and memory functions were impaired in neonatal mice following excitotoxic brain damage. Behavioral testing is useful in the evaluation of early developmental reflexes and long-term neurobehavioral outcome in neonatal mice with excitotoxic brain damage.