Factors influencing C-reactive protein status on admission in neonates after birth.

OBJECTIVE: To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth. METHODS: 820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth. RESULTS: A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35-4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15-13.07, P < 0.001) were independent risk factors for CRP ≥ 8 mg/L. Cesarean delivery (OR 0.40, 95%CI: 0.26-0.60, P < 0.001) was independent protective factor for CRP ≥ 8 mg/L. (2) Threshold effect analysis: A non-linear relationship was found between GA and CRP. When GA is less than 33.9 weeks, the risk of CRP ≥ 8 mg/L was reduced by 28% with one week increased (P < 0.001), and when GA is more than 33.9 weeks, the risk of CRP ≥ 8 mg/L was increased by 61% with one week increased (P < 0.001). CONCLUSIONS: GA, PROM, maternal autoimmune diseases and cesarean delivery were all independent influences neonatal CRP ≥ 8 mg/L on admission, and there was a nonlinear relationship between GA and neonatal CRP ≥ 8 mg/L on admission.

The association between sex and neonatal respiratory distress syndrome.

BACKGROUND: To investigate the association between sex and neonatal respiratory distress syndrome (NRDS). METHODS: Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates' data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered. RESULTS: 452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P < 0.05) after controlling for the confounding effects of GA, birth weight, WBC, PLT, CRP, total IgM, GDM, antenatal steroids use, meconium-stained amniotic fluid, and PPROM. CONCLUSIONS: Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.

A Novel Nomogram Based on Quantitative MRI and Clinical Features for the Prediction of Neonatal Intracranial Hypertension.

Intracranial hypertension (ICH) is a serious threat to the health of neonates. However, early and accurate diagnosis of neonatal intracranial hypertension remains a major challenge in clinical practice. In this study, a predictive model based on quantitative magnetic resonance imaging (MRI) data and clinical parameters was developed to identify neonates with a high risk of ICH. Newborns who were suspected of having intracranial lesions were included in our study. We utilized quantitative MRI to obtain the volumetric data of gray matter, white matter, and cerebrospinal fluid. After the MRI examination, a lumbar puncture was performed. The nomogram was constructed by incorporating the volumetric data and clinical features by multivariable logistic regression. The performance of the nomogram was evaluated by discrimination, calibration curve, and decision curve. Clinical parameters and volumetric quantitative MRI data, including postmenstrual age (p = 0.06), weight (p = 0.02), mode of delivery (p = 0.01), and gray matter volume (p = 0.003), were included in and significantly associated with neonatal intracranial hypertension risk. The nomogram showed satisfactory discrimination, with an area under the curve of 0.761. Our results demonstrated that decision curve analysis had promising clinical utility of the nomogram. The nomogram, incorporating clinical and quantitative MRI features, provided an individualized prediction of neonatal intracranial hypertension risk and facilitated decision making guidance for the early diagnosis and treatment for neonatal ICH. External validation from studies using a larger sample size before implementation in the clinical decision-making process is needed.

Restrictive Use of Empirical Antibiotics Is Associated with Improved Short Term Outcomes in Very Low Birth Weight Infants: A Single Center, Retrospective Cohort Study from China.

Antibiotics are essential for treating neonatal sepsis, but abuse or inappropriate use of antibiotics have harmful adverse effects. The inappropriate use of antibiotics has led to the significant increase in bacterial antimicrobial resistance in the neonatal intensive care unit (NICU). The aim of this study was to retrospectively analyze the changes in antibiotic usages in a NICU after the implementation of an antibiotic stewardship program and to determine the impact of this implementation on the short-term clinical outcomes of very low birth weight (VLBW) infants. The antibiotic stewardship program was initiated in the NICU in early 2015. For analysis, all eligible VLBW infants born from 1 January 2014 to 31 December 2016 were enrolled, and we classified the year 2014 as pre-stewardship, 2015 as during stewardship, and 2016 as post-stewardship. A total of 249 VLBW infants, including 96 cases in the 2014 group, 77 cases in the 2015 group, and 76 cases in the 2016 group, were included for final analysis. Empirical antibiotics were used in over 90% of VLBW infants in all three groups during their NICU stay. Over the 3-year period, the duration of an initial antibiotic course was significantly reduced. The proportion of patients receiving an initial antibiotic course for ≤3 days gradually increased (2.1% vs. 9.1% vs. 38.2%, p < 0.001), while the proportion of babies treated with an initial antibiotic course >7 days significantly decreased (95.8% vs. 79.2% vs. 39.5%, p < 0.001). The total days of antibiotic usage during the entire NICU stay also showed a significant reduction (27.0 vs. 21.0 vs. 10.0, p < 0.001). After adjusting for confounders, the reduction in antibiotic usage was associated with decreased odds of having an adverse composite short-term outcome (aOR = 5.148, 95% CI: 1.598 to 16.583, p = 0.006). To assess the continuity of antibiotic stewardship in the NICU, data from 2021 were also analyzed and compared to 2016. The median duration of an initial antibiotic course further decreased from 5.0 days in 2016 to 4.0 days in 2021 (p < 0.001). The proportion of an initial antibiotic course in which antibiotics were used for ≤3 days increased (38.2% vs. 56.7%, p = 0.022). Total antibiotic usage days during the entire NICU stay also decreased from 10.0 days in 2016 to 7.0 days in 2021 (p = 0.010). The finding of this study strongly suggests that restricting antibiotic use in VLBW infants is beneficial and can be achieved safely and effectively in China.

[Effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks]. / æŠ—ç”Ÿç´ ä½¿ç”¨ç­–ç•¥æ”¹è¿›å¯¹èƒŽé¾„<35周早产儿近期临床结局的影响.

OBJECTIVES: To study the effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks. METHODS: The medical data were retrospectively collected from 865 preterm infants with a gestational age of <35 weeks who were admitted to the Neonatal Intensive Care Unit of Xiangya Hospital of Central South University from January 1, 2014 to December 31, 2016. The improved antibiotic use strategy was implemented since January 1, 2015. According to the time of implementation, the infants were divided into three groups: pre-adjustment (January 1, 2014 to December 31, 2014; n=303), post-adjustment Ⅰ (January 1, 2015 to December 31, 2015; n=293), and post-adjustment Ⅱ (January 1, 2016 to December 31, 2016; n=269). The medical data of the three groups were compared. RESULTS: There were no significant differences among the three groups in gestational age, proportion of small-for-gestational-age infants, sex, and method of birth (P>0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had a significant reduction in the rate of use of antibiotics and the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days or 4-7 days and a significant reduction in the proportion of infants with a duration of antibiotic use of >7 days in the early postnatal period (P<0.05). Compared with the post-adjustment Ⅰ group, the post-adjustment Ⅱ group had a significant reduction in the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days and a significant reduction in the proportion of infants with a duration of antibiotic use of 4-7 days or >7 days (P<0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had significantly shorter duration of parenteral nutrition and length of hospital stay (P<0.05). There were gradual reductions in the incidence rates of grade ≥Ⅲ intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) after the adjustment of antibiotic use strategy. The multivariate logistic regression analysis showed that the adjustment of antibiotic use strategy had no effect on short-term adverse clinical outcomes, and antibiotic use for >7 days significantly increased the risk of adverse clinical outcomes (P<0.05). CONCLUSIONS: It is feasible to reduce unnecessary antibiotic use by the improvement in antibiotic use strategy in preterm infants with a gestational age of <35 weeks, which can also shorten the duration of parenteral nutrition and the length of hospital stay and reduce the incidence rates of grade ≥Ⅲ IVH and LOS.

D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate. / HSD17B4åŸºå› çªå˜è‡´D-双功能蛋白缺乏症.

A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the HSD17B4 gene. This article reports a case of D-bifunctional protein deficiency caused by HSD17B4 gene mutation and summarizes the epidemiological and clinical features, diagnosis, and treatment of this disease, with a focus on the differential diagnosis of this disease from Ohtahara syndrome.

Analyzing the Effects of Intrauterine Hypoxia on Gene Expression in Oocytes of Rat Offspring by Single Cell Transcriptome Sequencing.

Intrauterine hypoxia is one of the most frequently occurring complications during pregnancy, and the effects of antenatal hypoxia in offspring are not restricted to the perinatal period. Previous studies have reported on this phenomenon, which is usually described as multigenerational or transgenerational inheritance. However, the exact mechanism of this type of inheritance is still not clear. Therefore, in the present study, we investigated the alteration in the gene expression of oocytes, derived from intrauterine hypoxia rats and their offspring, by transcriptome sequencing. Our results showed that 11 differentially expressed genes were inherited from the F1 to F2 generation. Interestingly, these differentially expressed genes were enriched in processes predominantly involved in lipid and insulin metabolism. Overall, our data indicated that alteration in the gene expression of oocytes may be associated with some metabolic diseases and could potentially be the basis of transgenerational or multigenerational inheritance, induced by an adverse perinatal environment.

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia.

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

Risk Factors Related to Peripherally Inserted Central Venous Catheter Nonselective Removal in Neonates.

We aimed to investigate the incidence and risk factors associated with nonselective removal of peripherally inserted central venous catheter (PICC) in neonates. In this prospective cohort study, neonates who underwent PICC placement at neonatal intensive care units (NICUs) in China from October 2012 to November 2015 were included. The patient demographics, catheter characteristics, catheter duration, PICC insertion site, indication for PICC insertion, infuscate composition, PICC tip location, and catheter complications were recorded in a computerized database. Risk factors for nonselective removal were analyzed. A total of 497 PICCs were placed in 496 neonates. Nonselective removal occurred in 9.3% of PICCs during 10,540 catheter-days (4.6 nonselective removals per 1,000 catheter-days). These included occlusion (3%), infection (1.4%), leakage (2.0%), phlebitis (0.6%), displacement (1%), pleural effusion(0.6%), and breaks (0.6%). Noncentral tip position was independently associated with an increased risk of nonselective removal (odds ratio 2.621; 95% confidence interval, 1.258-5.461) after adjusting for gestational age, sex, birth weight, and PICC dwell time. No significant differences in the rate of complications occurred between silastic and polyurethane PICC or different insertion sites. Noncentral PICC tip position was the only independent risk factor for nonselective removal of PICC.

Excessive Activation of NMDA Receptors Induced Neurodevelopmental Brain Damage and Cognitive Deficits in Rats Exposed to Intrauterine Hypoxia.

Intrauterine hypoxia is one of the most common stressors in fetuses, which can lead to abnormal brain development and permanent neurological deficits in adulthood. Neurological disorder excitotoxicity induced by hypoxia or ischemia may involve N-methyl-D-aspartate receptors (NMDARs), which are known to participate in the maturation and plasticity of developmental neurons. Inhibition of NMDARs has been reported to improve neurological outcomes in traumatic brain injuries and Alzheimer's disease. Here, we investigated if antenatal blockade of NMDARs induced by memantine could alleviate neurodevelopmental brain damage and long-term cognitive deficits in intrauterine hypoxia rats. Pregnant rats were assigned to four groups: air control, air + memantine, hypoxia, and hypoxia + memantine. The rats were exposed to hypoxic conditions (FiO2 = 0.095-0.115) for 8 h/day (hypoxia group) or given a daily memantine injection (5 mg/kg, i.p.) before hypoxia exposure from pregnant day 19 (G19) to G20 (hypoxia + memantine group).The influence of NMDARs antenatal blockade by memantine on intrauterine hypoxia-induced brain developmental damage and cognitive function was then studied. Intrauterine hypoxia resulted in decreased fetal body weight, brain weight, cognitive function, hippocampal neuron numbers, and Ki-67 proliferation index in the hippocampus. Memantine preventive treatment in pregnant rats before hypoxia exposure alleviated the aforementioned damage in vivo. Excessive activation of NMDARs contributes to fetal brain developmental damage and cognitive ability impairment induced by intrauterine hypoxia, which could be alleviated by antenatal memantine preventative treatment.

The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production.

Studies have suggested that endogenous glutamate and N-methyl-d-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines. Although the expressions of NMDARs were different between MRC-5 and HFL-1, 1mM NMDA elicited the same trend in the downregulation of NR2A expression, the upregulation of NR2D, and the increase of cells proliferation and collagen production. Glutamate stimulation after 24-h of NMDA exposure resulted in weaker and more delayed but more prolonged iCa2+ elevation in HFL-1 than no NMDA exposed cells. NMDA increased the level of pERK1/2, cells proliferation and collagen production, whereas nonspecific NMDAR antagonist MK-801, NR2D-preferring receptor antagonist UBP141 and ERK1/2 phosphorylation inhibitor U0126 suppressed it, respectively. In conclusion, we found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism.

N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats.

BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions. RESULTS: Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes. CONCLUSIONS: NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.

N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro.

Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs) are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR's expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E) 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801's influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA's direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.