Neurodevelopmental Impairment In Preterm Infants Research Articles

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.

Association between bronchopulmonary dysplasia and death or neurodevelopmental impairment at 3 years in preterm infants without severe brain injury.

We investigated the association between bronchopulmonary dysplasia (BPD) and 3 years death or neurodevelopmental impairment (NDI) in very preterm infants without severe brain injury. Our prospective cohort study recruited preterm infants who were born prior to 32 weeks of gestational age and survived in the neonatal intensive care unit until 36 weeks of corrected age. Upon reaching 3 years of age, each infant was assessed for death or NDI such as cerebral palsy, cognitive deficit, hearing loss, and blindness. Correlations between BPD and death or NDI were determined using multiple logistic regression analyses adjusted for confounding factors. A total of 1,417 infants without severe brain injury who survived until 36 weeks of corrected age were initially enrolled in the study. Over the study period, 201 infants were lost to follow-up and 5 infants were excluded. Our final dataset, therefore, included 1,211 infants, of which 17 died after 36 weeks of corrected age and 1,194 were followed up to 3 years of age. Among these infants, 337 (27.8%) developed BPD. Interestingly, by 3 years of age, BPD was demonstrated to be independently associated with death or NDI, with an adjusted odds ratio of 1.935 (95% confidence interval: 1.292-2.899, p = 0.001), in preterm infants without severe neonatal brain injury. Our findings indicate that BPD is strongly associated with death or NDI in preterm infants without severe neonatal brain injury at 3 years of age. Further research is needed to understand the mechanisms linking the development of BPD with death or NDI and whether appropriate treatment of BPD may ameliorate or prevent the development of neurological complications.

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.

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.

Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study

To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

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.

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.

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.

Altered microstructure of the splenium of corpus callosum is associated with neurodevelopmental impairment in preterm infants with necrotizing enterocolitis

BackgroundNecrotizing enterocolitis (NEC) is a devastating disease in preterm infants with significant morbidities, including neurodevelopmental impairment (NDI). This study aimed to investigate whether NEC is associated with (1) brain volume expansion and white matter maturation using diffusion tensor imaging analysis and (2) NDI compared with preterm infants without NEC.MethodsWe included 86 preterm infants (20 with NEC and 66 without NEC) with no evidence of brain abnormalities on trans-fontanelle ultrasonography and magnetic resonance imaging at term-equivalent age (TEA). Regional brain volume analysis and white matter tractography were performed to study brain microstructure alterations. NDI was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III) at 18 months of corrected age (CA).ResultsPreterm infants with NEC showed significantly high risk of motor impairment (odds ratio 58.26, 95% confidence interval 7.80–435.12, p < 0.001). We found significantly increased mean diffusivity (MD) in the splenium of corpus callosum (sCC) (p = 0.001) and the left corticospinal tract (p = 0.001) in preterm infants with NEC. The sCC with increased MD showed a negative association with the BSID-III language (p = 0.025) and motor scores (p = 0.002) at 18 months of CA, implying the relevance of sCC integrity with later NDI.ConclusionThe white matter microstructure differed between preterm infants with and without NEC. The prognostic value of network parameters of sCC at TEA may provide better information for the early detection of NDI in preterm infants.

A Prediction Model for Short-Term Neurodevelopmental Impairment in Preterm Infants with Gestational Age Less than 32 Weeks

A Prediction Model for Short-Term Neurodevelopmental Impairment in Preterm Infants with Gestational Age Less than 32 Weeks

Long-term neurodevelopmental outcomes among preterm infants born to mothers with diabetes mellitus.

The long-term effects of maternal diabetes on preterm infant neurodevelopment are unknown. This study aims to determine if there was an increased likelihood of neurodevelopmental impairment in preterm infants born to mothers with diabetes. A retrospective cohort study was conducted on preterm infants with neurodevelopmental evaluations at 18-36 months corrected age using the Bayley Scales of Infant and Toddler Development Third edition. 680 former preterm infants were evaluated. There was no difference in cognitive, language, and motor scores. Infants born to diabetic mothers with AMA were significantly different in cognitive (adjusted-β (a-β),-7.24 [95%CI, -11.719 to -2.769]; P = 0.002) and language domains (a-β,-7.783 [95%CI, -13.603 to -1.963]; (P = 0.009). There was no significant difference in neurodevelopmental outcomes of preterm infants exposed to maternal diabetes. Preterm infants born to mothers with diabetes and AMA demonstrated lower cognitive and language scores at 2 years corrected age.

Hyperoxia Leads to Transient Endocrine Alterations in the Neonatal Rat During Postnatal Development

Introduction: High oxygen concentrations have been identified as one factor contributing to the pathogenesis of the retinopathia of prematurity, chronic lung disease of the preterm infant and preterm brain injury. Preterm infants also show short- and long-term alterations of the endocrine system. If hyperoxia is one pathogenetic factor has not been investigated yet. With regard to the high prevalence of neurodevelopmental impairments in preterm infants, the hypothalamus-pituitary-thyroid (HPT) axis, the hypothalamus-pituitary-adrenal (HPA) axis and the hypothalamus-pituitary-somatotropic (HPS) axis are of special interest due to their important role in neurodevelopment.Objective: The aim of this study was to investigate the effect of hyperoxia on the endocrine system in the neonatal rat by analyzing the activities of the HPT, HPA and HPS axes, respectively.Methods: Three-days old Wistar rats were exposed to hyperoxia (oxygen 80%, 48 h). On postnatal day 5 (P5) and P11, transcript levels of thyroid-stimulating hormone (TSH), proopiomelanocortin and growth hormone (GH) were analyzed in pituitary sections by in situ hybridization. Serologic quantification of TSH and thyroxine (T4), adrenocorticotropic hormone and GH were performed by Multiplex analysis and Enzyme-linked Immunosorbent Assay.Results: At P5, significantly lower GH levels were observed in pituitaries (mRNA) and in sera of rats exposed to hyperoxia. Serum TSH was significantly elevated without changes in T4.Conclusion: This is the first study demonstrating transient endocrine alterations following hyperoxia in the neonatal rat making oxygen a possible contributor to the pathogenesis of endocrine alterations seen in preterm infants. Considering the detrimental multi-organ effects of hyperoxia on the immature organism, a rational use of therapeutic oxygen in the treatrnent of preterm infants is of utmost importance.

Factors associated with neurodevelopment in preterm infants with systematic inflammation

BackgroundSeveral studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.MethodsThis prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.ResultsThe I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score − 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.ConclusionsSystemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment.

Does high-dose erythropoietin decrease the risk of death or severe neurodevelopmental impairment in preterm infants?

Does high-dose erythropoietin decrease the risk of death or severe neurodevelopmental impairment in preterm infants?

Unsatisfactory Short-Term Neurodevelopmental Outcomes of Preterm Infants Who Received Polymyxin B-Immobilized Fiber Column-Direct Hemoperfusion for Septic Shock.

Sepsis and septic shock are associated with high mortality and neurodevelopmental impairment in preterm infants. Recently, endotoxin and mediator removal using a polymyxin B-immobilized fiber column for direct hemoperfusion (PMX-DHP) has been used for the management of septic shock even in neonates. Although early withdrawal from shock with PMX-DHP contributes to survival, its effect on neurodevelopment after discharge is unclear. This study aimed to examine short-term neurodevelopmental impairment in preterm infants with septic shock who were treated with PMX-DHP. We retrospectively assessed five infants who received treatment with PMX-DHP (median 25.5 [interquartile range: 24.8-28.3] weeks and 817 [interquartile range: 667-954] g). Neurodevelopmental outcomes were assessed with the Kyoto Scale of Psychological Development 2001 at a median 34.5 (interquartile range: 29.5-44.5) months of corrected age after discharge. The short-term neurodevelopmental prognosis of preterm infants treated with PMX-DHP for septic shock was delayed (overall developmental quotient < 70) with an average quotient of 57.3. Furthermore, four (80%) of five patients presented with intraventricular hemorrhage and another four (80%) with periventricular leukomalacia. In conclusion, preterm infants with septic shock treated with PMX-DHP had unsatisfactory short-term neurodevelopmental outcomes. Hence, the effect of PMX-DHP in improving neurodevelopmental prognosis even in preterm infants with septic shock should be further evaluated.

Impact of multiple placental pathologies on neonatal death, bronchopulmonary dysplasia, and neurodevelopmental impairment in preterm infants.

BackgroundTo determine the association of placental pathology, including multiple placental lesions, with the occurrence and severity of bronchopulmonary dysplasia (BPD), death, and neurodevelopmental impairment (NDI) in preterm infants.MethodA retrospective cohort study of neonates <29 weeks gestational age (GA) born at Parkland Hospital from 08/2009 to 08/2012. Infants were stratified as follows: Group 1: no significant placental pathology; Group 2: single significant placental lesion; and Group 3: ≥2 placental lesions (multiple lesions). Primary outcome was death and/or BPD. Two-year neurodevelopmental follow-up was compared.ResultsIn all, 42% (100/241) of infants had one placental lesion, and 34% (82/241) ≥2 lesions. As the number of the pathologic lesions increased (no lesions vs. 1 vs. ≥2), the occurrence of death or BPD increased (25%, 37%, and 52%, respectively; P = 0.004). Moreover, infants with multiple pathologic lesions were more likely to have NDI (29%, 29%, and 46%, respectively; P = 0.03). After logistic regression, infants with multiple pathologic lesions were more likely to develop moderate-to-severe BPD [P < 0.01; OR 3.9 (1.5–10.1)] but not NDI.Conclusion(s)Neonates <29 weeks GA with multiple placental pathologic lesions have an increased risk for developing BPD, suggesting an interaction between placental inflammation and vascular pathology and the pathogenesis of BPD; however, the risk of NDI is not increased.

TNF-\u03b1 antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats

BackgroundSystemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α (TNF-α) plays important roles in systemic inflammation and local inflammation leading to apoptosis of premyelinating oligodendrocytes and white matter injury (WMI) in brain tissue. This study was conducted to investigate whether etanercept, a TNF-α antagonist, could attenuate systemic lipopolysaccharide (LPS)-induced WMI in the immature brain.ResultsWe found that intraperitoneal LPS administration caused systemic and local inflammation in brain tissue. Subsequent etanercept treatment significantly attenuated LPS-induced inflammation in brain tissue as well as in systemic circulation. Intraperitoneal LPS also induced microgliosis and astrocytosis in the cingulum and etanercept treatment reduced LPS-induced microgliosis and astrocytosis. Additionally, systemic LPS-induced apoptosis of oligodendrocyte precursor cells was observed, which was lessened by etanercept treatment. The concentration of etanercept in the CSF was higher when it was administrated with LPS than when administrated with a vehicle.ConclusionsIt appears that etanercept reduce WMI in the neonatal rat brain via attenuation of systemic and local inflammation. This study provides preclinical data suggesting etanercept-mediated modulation of inflammation as a promising approach to reduce WMI caused by sepsis or necrotizing enterocolitis in preterm infants.

Weight, Length, and Head Circumference Z-scores at 36 Weeks Are Not Accurate in Predicting Neurodevelopmental Impairment in Preterm Infants Less Than 30 Weeks Gestation (P11-062-19)

Abstract Objectives The association between poor growth and neurodevelopmental impairment (NDI) among preterm infants is well-established whether due to inadequate nutrition, adverse events or both. The present study assessed the diagnostic accuracy of 36-week anthropometric measures, including corresponding &lt; 10th and &lt; 3rd percentile cut points to predict NDI in preterm infants. Methods This study included data from the PreM Growth Cohort Study for preterm infants &lt; 30 weeks of gestational age (GA) and birth weights &lt; 1500 grams. The accuracy with which measured weight, length and head circumference z-scores can predict cognitive impairment (Bayley-III Cognitive Composite score &lt; 80) at 21 months corrected age (born in 2005–2014) and intellectual impairment (Wechsler Preschool and Primary Scale of Intelligence-3rd and 4th Edition (Intellectual test) score &lt; 70) at 3-years corrected age (born in 2001–2014) was determined by the area under the receiver operating characteristic curve (AUROC). Results At 21 months 98/621 (15.8%) of infants had low Bayley scores and 57/613 (9.3%) had low Intellectual test scores at 3 years. None of the AUROCs exceeded 0.6 and none were significantly different from 0.5. Sensitivities and specificities for the 10th and 3rd percentile cut points were equally poor, with most not exceeding 70% (Figures). The findings were similar between the Fenton 2013 and INTERGROWTH 2015 growth charts. The addition of morbidities increased the accuracy of predicting cognitive impairments except for infants with cerebral palsy, other morbidities had relatively marginal associations with impairment. Conclusions Preterm infant measures of weight, length, and head circumference z-scores at 36 weeks, including corresponding &lt; 10th and &lt; 3rd percentile cut points, are not accurate as predictors of NDI. This study confirms previous findings that preterm infants show some “catch up” in weight relative to growth references between 37–44 weeks GA. ClinicalTrials.gov Identifier: NCT03064022 Funding Sources Canadian Foundation for Dietetic Research. Supporting Tables, Images and/or Graphs