Vitamin D suppresses ferroptosis and protects against neonatal hypoxic-ischemic encephalopathy by activating the Nrf2/HO-1 pathway.

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death, and vitamin D (VD) is a neuroprotection nutrition whose deficiency is associated with its risk. However, the mechanism of VD involved in neonatal HIE is not well known. Methods: In this experiment a hypoxic-ischemic brain damage (HIBD) model was established by using the Rice-Vannucci method, rats were intraperitoneally injected with 0.1 µg/kg VD every day for two weeks. The brain damage and mitochondria injury were examined by hematoxylin-eosin (HE) staining and transmission electron microscope (TEM), respectively. The oxidation response and inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA), and the cell viability was determined by Cell Counting Kit-8 (CCK-8). mRNA and protein expression were detected by quantitative real real-time PCR (qRT-PCR), Western blot, and immunofluorescence. Results: The results showed VD effectively ameliorated brain histologic damage and mitochondria injury induced by hypoxic ischemia (HI). VD elevated the expression of Nrf2 and HO-1, which resulted in increased levels of GPX4, superoxide dismutase (SOD), and glutathione (GSH) and reduced content of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting in decreased ferroptosis in HI-treated rats. Moreover, VD reduced the secretion of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß. Conclusions: VD suppresses ferroptosis through activation of the Nrf2/HO-1 signaling pathway and exerts a protective role in neonatal HIE.

Effect of different maintenance doses of caffeine citrate on ventilator weaning in very preterm infants with respiratory distress syndrome: a prospective randomized controlled trial. / ä¸åŒç»´æŒå‰‚é‡æž¸æ©¼é ¸å’–å•¡å› å¯¹æžæ—©äº§å„¿å‘¼å¸çª˜è¿«ç»¼åˆå¾æ’¤æœºå½±å“ï¼šå‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the effect of different maintenance doses of caffeine citrate on the success rate of ventilator weaning in very preterm infants (gestational age of ≤32 weeks) with respiratory distress syndrome (RDS). METHODS: A total of 162 preterm infants with RDS who were admitted to the hospital from January 2016 to December 2018 were enrolled in this prospective trial. These infants had a gestational age of ≤32 weeks and required invasive mechanical ventilation. They were randomly divided into a high-dose caffeine group and a low-dose caffeine group, with 81 infants in each group. Within 6 hours after birth, both groups were given caffeine at a dose of 20 mg/kg. After 24 hours, the high- and low-dose caffeine groups were given caffeine at a maintenance dose of 10 mg/kg and 5 mg/kg, respectively. The two groups were compared in terms of re-intubation rate within 48 hours after ventilator weaning, durations of ventilation and oxygen therapy, enteral feeding, weight gain, and the incidence rates of complications and adverse reactions during hospitalization. RESULTS: The high-dose caffeine group had a significantly lower re-intubation rate within 48 hours after ventilator weaning than the low-dose caffeine group (P<0.05), with frequent apnea as the main reason for failed ventilator weaning in both groups. The high-dose caffeine group had significantly shorter durations of mechanical ventilation and oxygen therapy than the low-dose caffeine group (P<0.05). There were no significant differences between the two groups in the time to total enteral feeding, average daily weight gain, body weight at discharge, and the incidence rates of complications (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intracranial hemorrhage) and adverse reactions (tachycardia, hypertension, and feeding intolerance) (P>0.05). CONCLUSIONS: A high maintenance dose of caffeine can safely and effectively reduce the incidence rate of apnea after ventilator weaning and the failure rate of ventilator weaning in RDS preterm infants with a gestational age of ≤32 weeks, and therefore, it holds promise for clinical application.

[Early intellectual developmental outcome of late preterm infants].

OBJECTIVE: To investigate the early intellectual developmental outcome of late preterm infants. METHODS: A total of 106 late preterm infants with a gestational age of 34-36+6 weeks who were admitted to the neonatal ward between January 2012 and January 2015, cured, discharged, and regularly followed up at the outpatient service for high-risk children were enrolled as the preterm group. A total of 120 healthy full-term infants during the same period were randomly selected as the term group. Neonatal behavioral neurological assessment (NBNA) was performed for late preterm infants at a corrected gestational age of 40 weeks and full-term infants at a gestational age of 40 weeks. The Gesell Developmental Scale was used for late preterm infants at a corrected age of 3, 6, and 12 months and full-term infants at an age of 3, 6, and 12 months. RESULTS: The preterm group had an NBNA score of <37 and a significantly lower NBNA score than the term group (P<0.05). At the corrected age of 3 months, the preterm group had significantly lower scores of gross motor, fine motor, and social competence than the term group (P<0.05). At the corrected age of 6 months, the preterm group had significantly lower scores of adaptability, gross motor, and fine motor than the term group (P<0.05). At the corrected age of 12 months, the preterm group had significantly lower scores of adaptability, gross motor, and social competence than the term group (P<0.05). CONCLUSIONS: Late preterm infants have early intellectual developmental delay. It is necessary to perform neurodevelopmental monitoring for late preterm infants.

Effect of bronchopulmonary dysplasia on early intellectual development in preterm infants.

BACKGROUND: The aim of this study was to investigate the effect of bronchopulmonary dysplasia (BPD) on the early intellectual development of preterm infants. METHODS: From 2011 to 2015, 83 preterm infants diagnosed with BPD were recruited to the BPD group, and 89 preterm infants without BPD and 98 healthy term infants were randomly recruited to the non-BPD and term group, respectively. Neural and intellectual development according to the Gesell Development Scale were evaluated and compared between groups at 0-3 months, 3-6 months, 6-9 months, and 9-12 months of adjusted age for preterm infants and real age for term infants. Multivariate logistic regression was used to determine the associations between BPD and adverse neurological outcomes at 9-12 months of adjusted age. RESULTS: Compared with term infants, preterm infants had significantly lower developmental quotients for adaptability, gross motor, fine motor, language and social skills. At follow up, deficits in one or more neurofunctions related to adaptability, gross motor, fine motor, language and social skills were significantly more frequent in preterm children with BPD than in those with no history of BPD. BPD was independently associated with adverse neurological outcome at 9-12 months of adjusted age in preterm infants. CONCLUSIONS: Early intelligence disturbances occurred significantly more frequently in BPD infants than in non-BPD infants. Monitoring of the development of the nervous system in BPD infants should be strengthened.

[Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation].

OBJECTIVE: To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). METHODS: A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. RESULTS: The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well. CONCLUSIONS: Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

[Risk factors for extrauterine growth retardation at discharge in premature infants].

OBJECTIVE: To study the incidence and risk factors for extrauterine growth retardation (EUGR) at discharge in premature infants. METHODS: A retrospective analysis was performed on 596 premature infants who were admitted to the neonatal intensive care unit between 2006 and 2010. These subjects were classified into EUGR (n=217) and non-EUGR groups (n=379) based on the body weight at discharge. The risk factors for the occurrence of EUGR were studied by multivariate logistic regression analysis. RESULTS: Based on the body weight, length, and head circumference, the incidence of EUGR at discharge was 36.4% (217 cases), 42.0% (250 cases), and 22.8% (136 cases), respectively. Low gestational age, low birth weight, intrauterine growth retardation (IUGR), delayed enteral feeding and complications of the respiratory system were identified as risk factors for EUGR (OR=6.508, 14.522, 5.101, 1.366, and 1.501, respectively). CONCLUSIONS: The incidence of EUGR might be greatly decreased by strengthening the perinatal care, reducing the incidence of premature delivery and IUGR, undertaking early enteral feeding, and actively preventing postnatal complications.

[Effects of recombinant human erythropoietin on neurointelligence development in very low birth weight infants].

OBJECTIVE: To evaluate the clinical effects of the early use of recombinant human erythropoietin (rhEPO) on the neurointelligence development in very low birth weight infants (VLBWI). METHODS: Seventy-eight VLBWI were divided into rhEPO treatment group (n=35) and control group (n=43) according to the choice of their parents. Neonatal behavioral neurological assessment (NBNA) was performed at 40 weeks of corrected gestational age. The Gesell Developmental Schedules were used for neurodevelopmental evaluation at 3, 6, and 12 months of corrected age. The abnormal rates of auditory brainstem response (ABR) and cranial ultrasound were evaluated at 6 months of corrected age. RESULTS: The rhEPO treatment group had significantly higher NBNA scores at 40 weeks of corrected gestational age than the control group (P<0.05). The adaptability at 3 months of corrected age, the gross motor, adaptability, and sociability at 6 months, and the gross motor, adaptability, fine motor, sociability, and language at 12 months were significantly better in the rhEPO treatment group than in the control group (P<0.05). The abnormal rates of ABR and cranial ultrasound in the rhEPO treatment group were significantly lower than in the control group at 6 months of corrected age (P<0.05). CONCLUSIONS: Early use of rhEPO can promote the early recovery of neurological symptoms and improve the cognitive, motor, and language abilities in VLBWI due to its protective effects on the nervous system.