Impairment In Preterm Infants Research Articles

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.

Non-surgical treatment of stage 4A retinopathy of prematurity

BackgroundRetinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections.MethodsTen eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes.ResultsThe study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects.DiscussionThis combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition.ConclusionCombined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

Does perinatal management have the potential to reduce the risk of intraventricular hemorrhage in preterm infants?

Intraventricular hemorrhage (IVH) is an important cause of neurodevelopmental impairment in preterm infants. A number of risk factors for IVH have already been proposed; however, some controversies regarding optimal perinatal management persist. This study aimed to identify perinatal and neonatal attributes associated with IVH in a representative population of preterm infants. Perinatal data on 1,279 very preterm infants (<32 weeks of gestation) admitted to a tertiary neonatal intensive care unit were analyzed. The records were assessed using univariate analysis and logistic regression model to evaluate the risk factors for any and high-grade IVH (grade III-IV according to the classification by Papile) within the first week after birth. The incidence of any IVH was 14.3% (183/1,279); the rate of low-grade (I-II) and high-grade (III-IV) IVH was 9.0% (115/1,279) and 5.3% (68/1,279), respectively. Univariate analysis revealed multiple factors significantly associated with intraventricular hemorrhage: lower gestational age and birth weight, absence of antenatal steroids, vaginal delivery, low Apgar score at 5 min, delivery room intubation, surfactant administration, high frequency oscillation, pulmonary hypertension, pulmonary hemorrhage, tension pneumothorax, persistent ductus arteriosus, hypotension and early onset sepsis. Logistic regression confirmed lower gestational age, vaginal delivery, ductus arteriosus and early onset sepsis to be independent predictors for any IVH. Pulmonary hemorrhage, tension pneumothorax and early onset sepsis were independent risk factors for high-grade IVH. Complete course of antenatal steroids was associated with a lower risk for any (odds ratio 0.58, 95% confidence interval 0.39-0.85; P = .006) and for high-grade intraventricular hemorrhage (odds ratio 0.36, 95% confidence interval 0.20-0.65; P < .001). The use of antenatal steroids and mode of delivery are crucial in the prevention of IVH; however, our study did not confirm the protective effect of placental transfusion. Severe respiratory insufficiency and circulatory instability remain to be powerful contributors to the development of IVH. Early detection and management of perinatal infection may also help to reduce the rate of brain injury and improve neurodevelopment in high-risk newborns.

Postural Control Measurements to Predict Future Motor Impairment in Preterm Infants: A Systematic Review.

Preterm infants are more likely to demonstrate developmental delays than fullterm infants. Postural measurement tools may be effective in measuring the center of pressure (COP) and asymmetry, as well as predicting future motor impairment. The objective of this systematic review was to evaluate existing evidence regarding use of pressure mats or force plates for measuring COP and asymmetry in preterm infants, to determine how measures differ between preterm and fullterm infants and if these tools appropriately predict future motor impairment. The consulted databases included PubMed, Embase, Scopus, and CINAHL. The quality of the literature and the risk of bias were assessed utilizing the ROB2: revised Cochrane risk-of bias tool. Nine manuscripts met the criteria for review. The postural control tools included were FSA UltraThin seat mat, Conformat Pressure-Sensitive mat, Play and Neuro-Developmental Assessment, and standard force plates. Studies demonstrated that all tools were capable of COP assessment in preterm infants and support the association between the observation of reduced postural complexity prior to the observation of midline head control as an indicator of future motor delay. Postural measurement tools provide quick and objective measures of postural control and asymmetry. Based on the degree of impairment, these tools may provide an alternative to standardized assessments that may be taxing to the preterm infant, inaccessible to therapists, or not sensitive enough to capture motor delays.

The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep

Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.

The miRNA transcriptome of cerebrospinal fluid in preterm infants reveals the signaling pathways that promote reactive gliosis following cerebral hemorrhage.

Germinal Matrix-Intraventricular Haemorrhage (GM-IVH) is one of the most common neurological complications in preterm infants, which can lead to accumulation of cerebrospinal fluid (CSF) and is a major cause of severe neurodevelopmental impairment in preterm infants. However, the pathophysiological mechanisms triggered by GM-IVH are poorly understood. Analyzing the CSF that accumulates following IVH may allow the molecular signaling and intracellular communication that contributes to pathogenesis to be elucidated. Growing evidence suggests that miRs, due to their key role in gene expression, have a significant utility as new therapeutics and biomarkers. The levels of 2,083 microRNAs (miRs) in 15 CSF samples from 10 infants with IVH were measured using miRNA whole transcriptome sequencing. Gene ontology (GO) and miR family analysis were used to uncover dysregulated signalling which were then validated in vitro in human foetal neural progenitor cells treated with IVH-CSF. Five hundred eighty-seven miRs were differentially expressed in the CSF extracted at least 2 months after injury, compared to CSF extracted within the first month of injury. GO uncovered key pathways targeted by differentially expressed miRs including the MAPK cascade and the JAK/STAT pathway. Astrogliosis is known to occur in preterm infants, and we hypothesized that this could be due to abnormal CSF-miR signaling resulting in dysregulation of the JAK/STAT pathway - a key controller of astrocyte differentiation. We then confirmed that treatment with IVH-CSF promotes astrocyte differentiation from human fetal NPCs and that this effect could be prevented by JAK/STAT inhibition. Taken together, our results provide novel insights into the CSF/NPCs crosstalk following perinatal brain injury and reveal novel targets to improve neurodevelopmental outcomes in preterm infants.

Permissive hypercapnia and oxygenation impairment in premature ventilated infants

AimIn permissive hypercapnia high levels of carbon dioxide (CO2) are tolerated in ventilated preterm infants to minimise lung injury, but hypercapnia could directly impair oxygenation. We aimed to quantify the association of elevated CO2 with oxygenation impairment in preterm infants by measuring the right-to-left shunt and the ventilation/perfusion (VA/Q) ratio. MethodsPre-existing datasets from preterm infants during the acute phase of respiratory distress syndrome or with evolving or established bronchopulmonary dysplasia were analysed. Non-invasive paired measurements of the fraction of inspired oxygen (FIO2) and transcutaneous oxygen saturation (SpO2) were used to calculate the degree of right-to-left shunt, right shift of the FIO2 versus SpO2 curve and the VA/Q. ResultsA total of 75 infants (43 male) with a median (IQR) gestational age of 26.4 (24.7–27.7) weeks were studied at 7 (2–31) days. Thirty-six infants (48 %) had an arterial partial pressure of CO2 (PaCO2) above 6 kPa. The PaCO2 was independently associated with the right shift of the curve [adjusted p < 0.001, unstandardised coefficient; 2.26, 95 % CI: 1.51–2.95] and the right-to-left shunt [adjusted p = 0.016, unstandardised coefficient; 1.86, 95 % CI: 0.36–3.36] after adjusting for confounders. An increase of the PaCO2 from 5 to 8 kPa, corresponded to a right shift of the curve of 20.2 kPa or a decrease in the VA/Q from 0.66 to 0.24. ConclusionsIncreased carbon dioxide levels were significantly associated with impaired oxygenation in preterm infants with respiratory distress syndrome or bronchopulmonary dysplasia.

Neurodevelopmental Outcome of Preterm Infants with Hypothyroidism

Background: Hypothyroidism is one of the most common causes of preventable intellectual disability and is common in preterm infants. Some studies have reported that developmental delay is still high in these patients despite appropriate treatment. Objectives: This study aimed to investigate the short-term neurodevelopmental outcome of preterm infants with thyroid dysfunction. Methods: This cohort study included 50 preterm infants with thyroid dysfunction requiring levothyroxine treatment (case group) and 50 age- and sex-matched healthy preterm infants with normal thyroid tests (control group). The patients were followed, and Ages and Stages Questionnaires (ASQ) (including five domains) were filled out at 6 and 12 months to evaluate the short-term neurodevelopmental outcome. Results: There was no statistically significant difference in gestational age, sex, and birth weight between the two groups (P-values = 0.648, 0.756, and 0.866, respectively). A total number of 4 (8%) and 7 (14%) of the case group and 1 (2.85%) and 2 (5.71%) of the control group had a possible neurodevelopmental delay based on the low score in at least one domain of ASQ at 6 and 12 months of age (P-values = 0.321 and 0.222, respectively). Treated hypothyroidism was not significantly associated with higher impaired neurodevelopmental outcomes (P-value = 0.236, Odd Ratio: 2.686, 95% CI: 0.523 - 13.787). Conclusions: In this study, the risk of neurodevelopmental impairment in preterm infants with hypothyroidism was similar to that of healthy preterm infants. Thus, these findings may confirm the adequacy of levothyroxine replacement therapy in preventing neurodevelopmental delay.

Periventricular Microglia Polarization and Morphological Changes Accompany NLRP3 Inflammasome-Mediated Neuroinflammation after Hypoxic-Ischemic White Matter Damage in Premature Rats.

White matter damage (WMD) is a primary cause of cerebral palsy and cognitive impairment in preterm infants, and no effective treatments are available. Microglia are a major component of the innate immune system. When activated, they form typical pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes and regulate myelin development and synapse formation. Therefore, they may play a pivotal role in hypoxic-ischemic (HI) WMD. Herein, we investigated neural inflammation and long-term microglia phenotypic polarization in a neonatal rat model of hypoxia-ischemia-induced WMD and elucidated the underlying pathophysiological processes. We exposed 3-day-old (P3) Sprague-Dawley rats to hypoxia (8% oxygen) for 2.5 hr after unilateral common carotid artery ligation. The activation of NLRP3 inflammatory bodies, microglia M1/M2 polarization, myelination, and synaptic development in our model were monitored 7, 14, and 21 days after birth. In addition, the Morris water maze test was performed on postnatal Day 28. We confirmed myelination disturbance in the periventricular white matter, abnormal synaptic development, and behavioral changes in the periventricular area during the development of HI WMD. In addition, we found an association between the occurrence and development of HI WMD and activation of the NLRP3 inflammasome, microglial M1/M2 polarization, and the release of inflammatory factors. NLRP3 inhibition can play an anti-inflammatory role by inhibiting the differentiation of microglia into the M1 phenotype, thereby improving myelination and synapse formation. In conclusion, microglia are key mediators of the inflammatory response and exhibit continuous phenotypic polarization 7-21 days after HI-induced WMD. This finding can potentially lead to a new treatment regimen targeting the phenotypic polarization of microglia early after HI-induced brain injury.

EVALUATION OF PERCEPTION OF EXTEROCEPTIVE SENSATIONS IN PRETERM NEONATES-A PILOT STUDY

Aim: Preterm infant is deprived of various in-utero sensory experiences which have been documented as risk factor for prevalence of broad range of neurodevelopmental impairment in preterm infants. The present study evaluates the pain processing pattern in preterm neonates with and without known abnormalities using the Premature Infant Pain Profile (PIPP)-a 7 indicator pain measure that include three behavioural (facial actions: brow bulge, eye squeeze and nasolabial furrow), two physiological (heart rate and oxygen saturation), and two contextual (gestational age and behavioural state). Method: Neonates were randomly observed for receiving one of the following procedures: Dry cotton swab for simple touch (T), Cold and warm water wet cotton swabs for recording temperature perceptions (Tp), venous puncture in the back of the hand (P), considered as a painful stimulus; or alcohol swab friction on the back of the hand (F), considered as a distressing but not painful stimulus. A neonatologist evaluated physiologic and behavioral pain parameters. The evaluation of the perception includes utilizing Neonatal Infant Pain Scale (NIPS) and PIPP. Results: The mean pain score is 8.04 which is considered as moderate as per PIPP table. The standard deviation is 3.517. The probability distribution of pain is normal. Conclusion: The pain perception according to the recorded score is moderate in the premature neonates and the perception score is comparatively high in preterm neonates with known abnormalities. The infants born at 29-31 weeks of gestational age group showed greatest changes in the hemodynamic patterns during exteroceptive painful stimulation. KEY WORDS: premature, neonates, Premature Infant Pain Profile, PIPP, Neonatal Infant Pain Scale, NIPS, preterm birth

Effects of Recombinant Human Erythropoietin Administration in Premature Infants with Severe Intraventricular Hemorrhage: A Single-Center Experience

Purpose: We investigated the effects of early postnatal administration of erythropoietin (EPO) on neurodevelopmental outcomes and morbidities in preterm infants with severe grades of intraventricular hemorrhage (IVH).Methods: We retrospectively reviewed the medical records of preterm infants of gestational age 23&lt;sup&gt;+0&lt;/sup&gt; weeks to 31&lt;sup&gt;+6&lt;/sup&gt; weeks, who were diagnosed with severe grades of IVH and received EPO over at least 2 weeks. We compared clinical characteristics, major complications, and neurodevelopmental impairment between the two groups. The primary outcome was severe neurodevelopmental impairment at 18 to 26 months of corrected age. Severe neurodevelopmental impairment was defined as a mental developmental index or psychomotor developmental index of &lt;70 on the Bayley Scales of Infant Development II or diagnosis of cerebral palsy.Results: The study included 33 preterm infants (mean gestational age 25.2±1.6 weeks and mean birth weight 775.1±224.5 g). EPO was administered at a dose of 400 or 1,000 IU/kg thrice weekly and was maintained over a mean period of 58.6± 25.9 days beginning from 10.7±6.9 days after birth. We observed no difference in perinatal characteristics between the EPO (n=14) and the control group (n=19). Similarly, severe neurodevelopmental impairment rates did not differ between the EPO (85.7%) and control groups (78.9%). The incidence of neonatal morbidities including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity was also similar between the EPO and control groups.Conclusion: Early administration of EPO did not reduce the risk of severe neurodevelopmental impairment in preterm infants with severe IVH.

Spontaneous movements as a prognostic tool of neurodevelopmental outcomes in preterm infants: a narrative review.

An estimated 15 million infants are born each year prematurely. Although the survival rate of preterm infants has increased with advances in perinatal and neonatal care, many of them still suffer from various complications. Since improving neurodevelopmental outcomes of preterm births are a crucial topic of interest, accurate evaluations should be preceded for the detection of high-risk infants for cerebral palsy. General movements are spontaneous movements involving the whole body as the expression of neural activity and can be an excellent biomarker of neural dysfunction caused by brain impairment in preterm infants. The predictive value of general movements with respect to cerebral palsy increases with continuous observation. Automated approaches for general movements based on machine learning can help to overcome the limited utilization of assessment tools due to their qualitative or semi-quantitative nature and high dependency on the skills and experience of the assessors. This review will cover each of these topics, from the summarization of normal and abnormal general movements to the recent advance of automatic approaches based on infantile spontaneous movements.

A prediction model for short-term neurodevelopmental impairment in preterm infants with gestational age less than 32 weeks.

Early identification and intervention of neurodevelopmental impairment in preterm infants may significantly improve their outcomes. This study aimed to build a prediction model for short-term neurodevelopmental impairment in preterm infants using machine learning method. Preterm infants with gestational age < 32 weeks who were hospitalized in The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, and were followed-up to 18 months corrected age were included to build the prediction model. The training set and test set are divided according to 8:2 randomly by Microsoft Excel. We firstly established a logistic regression model to screen out the indicators that have a significant effect on predicting neurodevelopmental impairment. The normalized weights of each indicator were obtained by building a Support Vector Machine, in order to measure the importance of each predictor, then the dimension of the indicators was further reduced by principal component analysis methods. Both discrimination and calibration were assessed with a bootstrap of 505 resamples. In total, 387 eligible cases were collected, 78 were randomly selected for external validation. Multivariate logistic regression demonstrated that gestational age(p = 0.0004), extrauterine growth restriction (p = 0.0367), vaginal delivery (p = 0.0009), and hyperbilirubinemia (0.0015) were more important to predict the occurrence of neurodevelopmental impairment in preterm infants. The Support Vector Machine had an area under the curve of 0.9800 on the training set. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the curve on the test set is 0.70. The external validation proves the reliability of the prediction model. A support vector machine based on perinatal factors was developed to predict the occurrence of neurodevelopmental impairment in preterm infants with gestational age < 32 weeks. The prediction model provides clinicians with an accurate and effective tool for the prevention and early intervention of neurodevelopmental impairment in this population.

TwinEDA: a sustainable deep-learning approach for limb-position estimation in preterm infants' depth images.

Early diagnosis of neurodevelopmental impairments in preterm infants is currently based on the visual analysis of newborns' motion patterns by trained operators. To help automatize this time-consuming and qualitative procedure, we propose a sustainable deep-learning algorithm for accurate limb-pose estimation from depth images. The algorithm consists of a convolutional neural network (TwinEDA) relying on architectural blocks that require limited computation while ensuring high performance in prediction. To ascertain its low computational costs and assess its application in on-the-edge computing, TwinEDA was additionally deployed on a cost-effective single-board computer. The network was validated on a dataset of 27,000 depth video frames collected during the actual clinical practice from 27 preterm infants. When compared to the main state-of-the-art competitor, TwinEDA is twice as fast to predict a single depth frame and four times as light in terms of memory, while performing similarly in terms of Dice similarity coefficient (0.88). This result suggests that the pursuit of efficiency does not imply the detriment of performance. This work is among the first to propose an automatic and sustainable limb-position estimation approach for preterm infants. This represents a significant step towards the development of broadly accessible clinical monitoring applications.

Assessment of Small for gestational age as a health risk for thyroid impairment in preterm infants

Assessment of Small for gestational age as a health risk for thyroid impairment in preterm infants

AFENet: Attention Fusion Enhancement Network for Optic Disc Segmentation of Premature Infants.

Retinopathy of prematurity and ischemic brain injury resulting in periventricular white matter damage are the main causes of visual impairment in premature infants. Accurate optic disc (OD) segmentation has important prognostic significance for the auxiliary diagnosis of the above two diseases of premature infants. Because of the complexity and non-uniform illumination and low contrast between background and the target area of the fundus images, the segmentation of OD for infants is challenging and rarely reported in the literature. In this article, to tackle these problems, we propose a novel attention fusion enhancement network (AFENet) for the accurate segmentation of OD in the fundus images of premature infants by fusing adjacent high-level semantic information and multiscale low-level detailed information from different levels based on encoder–decoder network. Specifically, we first design a dual-scale semantic enhancement (DsSE) module between the encoder and the decoder inspired by self-attention mechanism, which can enhance the semantic contextual information for the decoder by reconstructing skip connection. Then, to reduce the semantic gaps between the high-level and low-level features, a multiscale feature fusion (MsFF) module is developed to fuse multiple features of different levels at the top of encoder by using attention mechanism. Finally, the proposed AFENet was evaluated on the fundus images of preterm infants for OD segmentation, which shows that the proposed two modules are both promising. Based on the baseline (Res34UNet), using DsSE or MsFF module alone can increase Dice similarity coefficients by 1.51 and 1.70%, respectively, whereas the integration of the two modules together can increase 2.11%. Compared with other state-of-the-art segmentation methods, the proposed AFENet achieves a high segmentation performance.

A Birth Cohort Study of Neurodevelopmental Outcomes from Birth to 2 Years of Age in Preterm Infants under 34 Weeks of Gestation.

Background The tissues and organs of premature infants are immature and easily damaged by external adverse factors, leading to functional development disorders and abnormalities. Besides, the incidence of premature babies in various countries has an increasing trend, with the incidence rate exceeding 10%. Objective This study aims to investigate the neurodevelopment and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in premature infants under 34 weeks of gestation from birth to 2 years of age, so as to provide the basis for early intervention of premature infants in the clinic. Methods A cohort of premature infants was established using 263 premature infants with a gestational age of 28–33 + 6 weeks who were born alive from March 1, 2018, to February 28, 2019, in four tertiary hospitals in Shenzhen. In addition, 263 full-term infants of the same sex who were born in the same period in the four hospitals were randomly selected and paired in a ratio of 1 : 1 as the control group. The subjects were assessed for neurodevelopment using the Gesell test scale at 6, 12, 18, and 24 months after birth (premature infants were corrected for months). We calculated the neurodevelopmental indicators of children in each month of age and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in the two groups. Results The results of this study showed that the cohort of premature infants with birth gestational age less than 34 weeks had higher adaptive, fine motor, and personal-social energy domain development quotient (DQ) values from the corrected gestational age of 6 months to the corrected gestational age of 24 months after birth compared with the full-term cohort. And it also achieved catch-up growth in neurological development, but the detection rates of neurodevelopmental abnormalities at the corrected gestational age of 12 and 24 months were higher than those in the full-term cohort. Conclusion It is important to reduce the disability rate and degree of premature infants by strengthening the systematic management, early promotion and supervision, as well as early intervention for preterm infants with developmental abnormalities who were born at gestational age less than 34 weeks after birth.

Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic-ischemic white matter damage.

AimWhite matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic‐ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic‐ischemic WMD were evaluated.MethodsWe identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic‐ischemic WMD (HI), and HI+caffeine‐treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments.ResultsIn paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin‐associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic‐ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic‐ischemic WMD‐induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic‐ischemic WMD by preventing the HI‐induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK‐7.ConclusionCaffeine may have clinical applications in the management of prophylactic hypoxic‐ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.

Factors associated with neurodevelopmental impairment in preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication in preterm infants with very low birth weight and is known to lead to poor neurodevelopmental outcomes. This study aimed to identify factors associated with neurodevelopmental impairment (NDI) in patients with moderate to severe BPD. A total of 83 preterm infants born between 24- and 29-weeks' gestation who were admitted to the neonatal intensive care unit and developed moderate/severe BPD between 2013 and 2017 were retrospectively evaluated. Developmental assessment was performed at 18 to 24 months of corrected age using the Bayley Scales of Infant Development II (BSID-II). Patients with NDI (n=41) and without NDI (n=42) were compared. BSID-II Mental Development Index and Psychomotor Development Index scores were 87±11 and 83±8 in the non-NDI group and 57±12 and 52±8 in the NDI group, respectively (p<0.001). The NDI group had significantly lower birth weight (847±174 vs. 1012±192 g) and gestational age (26.1±1.3 and 27.6±1.6 weeks) compared to the non-NDI group (p<0.001). Intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, exposure to steroids, duration of respiratory support, and length of hospital stay were significantly higher in the NDI group (p<0.001). Many of the conditions in this study were found to be associated with poor neurodevelopmental outcomes in patients with BPD, such as prolonged respiratory support, prolonged hospitalization, intraventricular hemorrhage, retinopathy, and steroid therapy, can be avoided or prevented with strict protocols and prevention strategies. Appropriate management of comorbid risk factors may help prevent poor neurodevelopmental outcomes.