Neonatal Intraventricular Hemorrhage Research Articles

Development of a machine learning model for prediction of intraventricular hemorrhage in premature neonates.

Intraventricular hemorrhage (IVH) is a common and severe complication in premature neonates, leading to long-term neurological impairments. Early prediction and identification of risk factors for IVH in premature neonates are crucial for improving clinical outcomes. This study aimed to predict IVH in premature neonates and determine risk factors using machine learning (ML) algorithms. This study investigated the medical records of premature neonates admitted to the neonatal intensive care unit. The patients were labeled as case (IVH) and control (No IVH). The independent variables included demographic, clinical, laboratory, and imaging data. Machine learning algorithms, including random Forest, support vector machine, logistic regression, and k-nearest neighbor, were used to train the models after data preprocessing and feature selection. The performance of the trained models was evaluated using various performance metrics. Data from 160 premature neonates were collected including 70 patients with IVH. The identified risk factors for IVH were the gestational age, birth weight, low Apgar scores at 1min and 5min, delivery method, head circumference, and various laboratory findings. The random forest algorithm demonstrated the highest sensitivity, specificity, accuracy, and F1 score in predicting IVH in premature neonates, with a great area under the receiver operating characteristic curve of 0.99. This study revealed that the random forest model effectively predicted IVH in premature neonates. The early identification of premature neonates at higher risk of IVH allows for preventive measures and interventions to reduce the incidence and morbidity of IVH in these patients.

The role of stem cells in the management of neonatal posthemorrhagic hydrocephalus.

Neonatal intraventricular hemorrhage (IVH) is a common complication of prematurity as it affects 12.4% of preterm infants weighing under 1500g. Posthemorrhagic hydrocephalus (PHH) is an important complication of neonatal IVH and can have serious long-term consequences such as cognitive impairment and cerebral palsy. The purpose of this review is to determine whether stem cell transplantation can play a role in the treatment of neonatal IVH mainly focusing on the prevention of the catastrophic sequelae of neonatal IVH, as well as to the improve outcome of these patients. A literature search was performed using the PubMed/MEDLINE and Scopus databases, and after meticulous screening, eight articles were finally selected. The authors included both animal and human studies in this narrative review. Our review included eight articles, five animal studies and three human studies, including one phase 1 clinical trial, one pilot study, and one case report. Intraventricular transplantation of mesenchymal stem cells (MSCs) early after IVH diagnosis seems to prevent the development of PHH, improve myelination, and reduce periventricular cell death, inflammation, and reactive gliosis. It also seems to be a safe and well-tolerated procedure in preterm infants. Animal and human study findings regarding stem cell transplantation in the treatment of IVH show promising results in reducing the risk of PHH. Further research with larger series is needed to better determine its safety and efficacy. Larger studies such as randomized controlled trials could establish the efficacy and tolerability of the treatment.

Advancing the management of neonatal hemorrhages: clinical evaluation of external ventricular drainage efficacy.

To evaluate the clinical efficacy of external ventricular drainage (EVD) in the treatment of neonatal intraventricular hemorrhage (IVH). A retrospective analysis was conducted on the clinical data of neonates with IVH admitted to the Department of Neurosurgery at Qingdao Women and Children's Hospital from January 2018 to February 2024. All patients received a definitive diagnosis followed by EVD treatment. Regular follow-ups were conducted, and patients who developed posthemorrhagic hydrocephalus (PHH) underwent ventriculoperitoneal shunt (VPS) procedures. Among the 44 neonates with IVH, 28 were male and 16 were female. The median gestational age at birth was 36weeks (range: 24-40weeks), and the median birth weight was 2.9kg (range: 0.78-4.33kg). There were 3 cases of grade II IVH, 34 cases of grade III IVH, and 7 cases of grade IV IVH. The average duration of EVD was 12.2 ± 5.6days. All patients were followed up for at least 1year. Twelve patients (27%) developed hydrocephalus, of which 8 cases (18%) with progressive ventricular enlargement underwent VPS, and 4 cases (9%) had arrested hydrocephalus and remained stable without VPS. During the follow-up period, 39 patients exhibited normal development, 3 patients (6.8%) developed epilepsy, and 2 patients (4.5%) developed cerebral palsy. EVD is an effective treatment for intraventricular hemorrhage. It improves survival rates and outcomes for patients while effectively reducing the incidence of hydrocephalus.

Noninvasive optical monitoring of cerebral hemodynamics in a preclinical model of neonatal intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is a common complication in premature infants and is associated with white matter injury and long-term neurodevelopmental disabilities. Standard diagnostic tools such as cranial ultrasound and MRI are widely used in both preclinical drug development and clinical practice to detect IVH. However, these methods only provide endpoint assessments of blood accumulation and lack real-time information about dynamic changes in ventricular blood flow. This limitation could potentially result in missed opportunities to advance drug candidates that may have protective effects against IVH. In this pilot study, we aimed to develop a noninvasive optical approach using diffuse correlation spectroscopy (DCS) to monitor real-time hemodynamic changes associated with hemorrhagic and sub-hemorrhagic events in a preclinical rabbit model of IVH. DCS measurements were conducted during the experimental induction of IVH, and results were compared with ultrasound and histological analysis to validate findings. Significant changes in hemodynamics were detected in all animals subjected to IVH-inducing procedures, including those that did not show clear positive results on ultrasound. The study revealed progressively elevated coefficients of variation in blood flow, particularly driven by increased oscillations within the 0.05-0.1 Hz frequency band. These hemodynamic changes were more pronounced in animals that developed IVH, as confirmed by ultrasound. Our findings suggest that real-time optical monitoring with DCS can provide critical insights into pathological blood flow changes, offering a more sensitive and informative tool for evaluating potential therapeutics in the context of IVH.

A Care-bundle to Prevent Germinal Matrix–Intraventricular Hemorrhage in Neonates

A Care-bundle to Prevent Germinal Matrix–Intraventricular Hemorrhage in Neonates

Regional variations in morbidity and mortality among neonates with intraventricular hemorrhage: a national database analysis.

Intraventricular hemorrhage (IVH) often affects newborns of low gestational age and low birth weight, requires critical care for neonates, and is linked to long-term neurodevelopmental outcomes. Assessing regional differences in the U.S. in care for neonatal IVH and subsequent outcomes can shed light on ways to mitigate socioeconomic disparities. Using the 2016-2019 National Inpatient Sample (NIS), patients with a primary diagnosis of IVH were identified using ICD-10-CM codes. A retrospective cohort study was conducted with patients stratified by hospital region. Demographics, comorbidities, presentation, intraoperative variables, and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as > 75th percentile of LOS), exorbitant cost (defined as > 75th percentile of cost), and mortality. Included in this study were 1630 newborns with IVH. A larger portion of patients in the South and Midwest were Black, compared to the Northeast and West (Northeast: 12.2% vs Midwest: 30.2% vs South: 22.8% vs West: 5.8%, p < 0.001), while a greater percentage of patients in the West and South were Hispanic (Northeast: 7.3% vs Midwest: 9.5% vs South: 22.8% vs West: 36.2%, p < 0.001). LOS was similar among all regions. Factors associated with prolonged LOS included hydrocephalus and CSF diversions. Median total cost of admission was highest in the West, while the South was associated with decreased odds of exorbitant cost. LOS was associated with exorbitant cost, and large bed-volume hospital, VLBW, and permanent CSF shunt were associated with mortality. Demographic variables, but not presenting or intraoperative variables, differed among regions, pointing to possible geographic health disparities. The West had the highest total cost of admission, while the South was associated with reduced odds of exorbitant admission costs.

Insurance Disparities in Patient Outcomes and Healthcare Resource Utilization Following Neonatal Intraventricular Hemorrhage

Within the field of pediatric neurosurgery, insurance status has been shown to be associated with surgical delay, longer time to referral, and longer hospitalization in epilepsy treatment, myelomeningocele repair, and spasticity surgery.1,2 The aim of this study was to investigate the association of insurance status with inpatient adverse events, length of stay, and costs for newborns diagnosed with intraventricular hemorrhage (IVH). A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Patients with a primary diagnosis of IVH were identified using ICD-10-CM diagnostic and procedural codes. Patients were categorized based on insurance status: Medicaid or Private Insurance (PI). Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as >75th percentile of LOS) and exorbitant cost (defined as >75th percentile of cost). Demographics differed significantly between groups, with the majority of newborns in the PI cohort being White (Medicaid: 35.8% vs PI: 60.3%, p<0.001) and the majority of Medicaid patients being in the 0-25th quartile of household income (Medicaid: 40.9% vs PI: 12.9%, p<0.001). While insurance status was not independently associated with increased odds of extended LOS or exorbitant cost, Medicaid patients had a greater mean LOS and total cost of admission than PI patients. Demographic characteristics, mean LOS, and mean total cost differed significantly between Medicaid and PI patients, indicating potential disparities based on insurance status. However, insurance status was not independently associated with increased healthcare utilization, necessitating further research in this area of study.

Reduced racial disparities among newborns with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. Using the 2016-2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28days old (p = 0.008). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC (p < 0.001). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.

Frequency of Intraventricular Haemorrhage (IVH) in Early Preterm Neonates Born at DHQ Teaching Hospital Gujranwala

Objective: The reported frequency of intraventricular hemorrhage in preterm neonates varied greatly. We determined the frequency of IVH in premature neonates in the pediatric unit of DHQ Hospital Gujranwala. Materials &amp; Methods: This cross-sectional study involved 282 very low birth weight neonates (birth weight &lt;1500 gm.) delivered very preterm (gestational age &lt;32 weeks). These neonates were assessed for intraventricular hemorrhage which was diagnosed on cranial ultrasound performed on 3rd day of life. The frequency of IVH was compared across various attributing factors i.e., gestational age at delivery, gender, birth weight, mode of delivery, and maternal antenatal steroids. Results: The mean gestational age at delivery was 27.5±2.3 weeks while the mean birth weight was 1120.5±190.2 grams. 172 (61.0%) neonates were delivered vaginally while C-section was performed in 110 (39.0%) cases. 263 (93.3%) mothers received antenatal steroids. Intraventricular hemorrhage was diagnosed in 64 (22.7%) early preterm neonates. The frequency of IVH increased significantly with increasing prematurity; 24-27 weeks vs. 28-31 weeks (28.9% vs. 17.0%; p-value=0.017), decreasing birth weight; &lt;1 kg vs. ?1kg (31.8% vs. 18.6%; p-value=0.014) and lack of antenatal steroids (52.6% vs. 20.5%; p-value=0.001). Conclusion: The intraventricular hemorrhage was observed in 22.7% of early preterm neonates which advocates routine screening of preterm neonates for IVH so that timely identification and anticipated management may improve the outcome of such neonates. We also identified increasing prematurity, decreasing birth weight, and lack of antenatal steroids as potential attributing factors that can be used for risk stratification and management planning of such cases.

Evaluation of the effect of intraventricular haemorrhage on cerebral perfusion in preterm neonates using three-dimensional pseudo-continuous arterial spin labelling.

Intraventricular haemorrhage (IVH) often arises as a cerebral complication directly related to preterm birth. The impaired autoregulation of cerebral blood flow is closely associated with IVH in preterm neonates. Three-dimensional pseudo-continuous arterial spin labelling (3D-pCASL) is a noninvasive magnetic resonance imaging (MRI) technique used for evaluating cerebral perfusion. This study aimed to compare cerebral blood flow values among three distinct groups using 3D-pCASL: preterm neonates with and without IVH and preterm neonates at term-equivalent age. A total of 101 preterm neonates who underwent conventional MRI and 3D-pCASL were included in this study. These neonates were categorised into three groups: 12 preterm neonates with IVH, 52 preterm neonates without IVH, and 37 healthy neonates at term-equivalent age. Cerebral blood flow measurements were obtained from six brain regions of interest (ROIs)-the frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, and thalamus-in the right and left hemispheres. The cerebral blood flow values measured in all ROIs of preterm neonates with IVH were significantly lower than those of neonates at term-equivalent age (all P<0.05). Additionally, the cerebral blood flow in the temporal lobe was lower in preterm neonates without IVH than in neonates at term-equivalent age (16.87±5.01 vs. 19.76±5.47 ml/100 g/min, P=0.012). Furthermore, a noteworthy positive correlation was observed between post-menstrual age and cerebral blood flow in the temporal lobe (P=0.037), basal ganglia (P=0.010), and thalamus (P=0.010). The quantitative cerebral blood flow values, as measured by 3D-pCASL, highlighted that preterm neonates with IVH had decreased cerebral perfusion. This finding underscores the potential of 3D-pCASL as a technique for evaluating the developmental aspects of the brain in preterm neonates.

Early red blood cell transfusion and the occurrence of intraventricular hemorrhage in very preterm infants

BackgroundPreterm infants are at risk of developing both intraventricular hemorrhage (IVH) and anemia of prematurity. Several studies reported an association between early postnatal red blood cell (RBC) transfusion and IVH, however the timing and causality between these two remains unclear. AimsTo describe the temporal sequence between administration of early RBC transfusion (within the first week of life) and diagnosis of IVH in very preterm infants. Study designRetrospective single center case-series. Subjects132 very preterm infants (<32 weeks' gestation), admitted to a level III neonatal intensive care unit, studied with serial cranial ultrasound (CUS), and diagnosed with any grade of IVH. Outcome measuresNumber and timing of early RBC transfusions in relation to the timing of IVH. ResultsMedian time of IVH diagnosis was 20.5 h after birth (interquartile range [IQR], 6.25–49.00 h). Of those who received an early RBC transfusion (36 %, 47/132), only 15 % (20/132) received it before the IVH diagnosis. Infants with RBC transfusion before IVH more frequently had lower birth weight, received less fequently antenatal steroids, required more often invasive mechanical ventilation and surfactant administration, had more often hypo- and hypercapnia, and received more fluid boluses, NaHCO3, and inotropes compared to the rest. ConclusionsIn the majority of infants, IVH was already present at the time of the first RBC transfusion. Studies including pre- and post RBC transfusion CUS are needed to assess the effect of early RBC transfusions on the development of IVH in preterm neonates.

The relationship between mean platelet volume (MPV) and intraventricular hemorrhage in very low birth weight infants.

Intra ventricular hemorrhage (IVH) is a major cause of mortality among very low birth weight infants. This study aimed to investigate the relationship between mean platelet volume (MPV) and IVH in very low birth weight infants. In this cohort study, all premature infants weighing less than 1500 grams who were admitted to the NICU were enrolled from August 2018 to July 2019. Brain ultrasonography was performed on the first and seventh days and one month of age and were compared with Platelet count and MPV. From 183 neonates, 23 cases (12.6%) had IVH. The mean MPV on the first day in the group with IVH was 10.48±0.85 and in the non-IVH group was 9.9±0.74 (P = 0.005). The mean MPV on the seventh day in the IVH and non-IVH group were 10.4±0.92 and 10.03±0.74 (P = 0.04) respectively. On the first and seventh day, for one unit of MPV increase, the chance of IVH increased by 2.68 and 2.1 respectively. (p = 0.001; OR3.643; 95% CI [1.703-7.753]). The mean MPV index is significantly higher in the infants with IVH and therefore it can be used in early detection of IVH in neonates weighing less than 1500 grams.

Azithromycin reduces hemoglobin-induced innate neuroimmune activation

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to reduce innate immune activation in an in vitro model of microglial activation using the blood product hemoglobin (Hgb). We then utilized azithromycin in our in vivo model of IVH, using intraventricular blood injection into the lateral ventricle of post-natal day 5 rat pups. In both models, azithromycin modulated innate immune activation by several outcome measures including mitochondrial bioenergetic analysis, cytokine expression and flow cytometric analysis. This suggests that azithromycin, which is safe for neonates, could hold promise for modulating innate immune activation after IVH.

Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation.

Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation.

Timing of umbilical cord occlusion, delayed vs early, in preterm babies: A randomized controlled trial (CODE-P Trial)

IntroductionOur hypothesis was that delayed cord clamping (DCC) (not earlier than 30 s; at 30–60 s) in premature neonates (born between 26.0 and 32.6 weeks of gestation), as compared with the usual early cord clamping (ECC), significantly reduces the need for blood transfusions and incidence of intraventricular haemorrhage (IVH) without an increased rate of maternal postpartum haemorrhage. Material and methodsA prospective, open-label, randomized, controlled trial was conducted at Vall d’Hebron Hospital from July 2014 to December 2018. All pregnant women at risk of impending preterm birth (≥26.0-<33.0 weeks of gestation) who were admitted to the obstetrics emergency department were evaluated for eligibility. If they met the eligibility criteria, they were invited to participate in the study and, if they agreed, they signed an informed consent. Patients were randomly assigned to one of two groups: ECC group and DCC group. ResultsOur study included a total of 57 patients: 30 in the ECC group and 27 in the DCC group. Due to a lack of funding and low recruitment rates, the study was discontinued in 2018. Maternal characteristics and obstetric outcomes were similar between both groups. The intention-to-treat analysis did not reveal any differences between groups for neonatal red blood cell transfusions, neonatal IVH or maternal postpartum haemorrhage. There were no differences for secondary outcomes. Similarly, no differences were observed in the as-treated analysis. ConclusionThe primary and secondary outcomes of our study were not achieved. Therefore, more meta-analysis and trials are needed to evaluate the appropriate timing of cord clamping in preterm birth.

Reducing Severe Intraventricular Hemorrhage in Preterm Infants With Improved Care Bundle Adherence.

Intraventricular hemorrhage prevention bundles (IVHPBs) can decrease the incidence of intraventricular hemorrhage (IVH) in premature infants. Our center had a high rate of severe (grade III/IV) IVH (9.8%), and poor adherence (24%) to an IVHPB in neonates born ≤1250 g or ≤30 gestational weeks. Improvement initiatives were planned to decrease the incidence of severe IVH by 30% over 2 years. A multidisciplinary team undertook interventions including in-service training, prompt initiation of IVHPB, revision of guidelines, and process standardization. Baseline data were collected from May 2016 to June 2018, with interventions occurring from July 2018 to May 2020. Adherence to the IVHPB was the primary process measure, and incidence of severe IVH the primary outcome measure. Control charts were used to analyze the effect of interventions on outcome. Balancing measures included use of breast milk at discharge, use of mechanical ventilation after initial resuscitation, and bronchopulmonary dysplasia. A total of 240 infants were assessed preintervention, and 185 during interventions. Adherence to the IVHPB improved from 24% to 88%. During this period, the incidence of severe IVH decreased from 9.8% to 2.4%, a 76% reduction from baseline. A higher adherence score was associated with reduced odds of IVH (odds ratio 0.30; 95% confidence interval 0.10-0.90, P = .03). Interventions focused on enhancing adherence to an IVHPB were associated with a reduced rate of severe IVH in high-risk neonates, highlighting the importance of assessing adherence to clinical guidelines.

Neuroendoscopic Lavage and Third Ventriculostomy for the Treatment of Intraventricular Hemorrhage and Hydrocephalus in Neonates. A Prospective Study with 18 Months of Follow-Up.

Neonatal intraventricular hemorrhage (IVH) may evolve into posthemorrhagic hydrocephalus and cause neurodevelopmental impairment, becoming a common complication of premature infants, occurring in up to 40% of preterm infants weighing less than 1,500 g at birth. Around 10 to 15% of preterm infants develop severe (grades III-IV) IVH. These infants are at high risk of developing posthemorrhagic hydrocephalus. Neuroendoscopic lavage (NEL) is a suitable alternative for the management of this pathology. In this study, an endoscopic surgical approach directed toward the removal of intraventricular hematoma was evaluated for its safety and efficacy. Between August 2016 and December 2019 (29 months), 14 neonates with posthemorrhagic hydrocephalus underwent NEL for removal of intraventricular blood by a single senior neurosurgeon. Complications such as reintervention and ventriculoperitoneal (VP) shunt placement were evaluated prospectively with an 18-month follow-up on average. In total, 14 neonates with IVH grades III and IV were prospectively recruited. Of these, six neonates did not need a VP shunt in the follow-up after neuroendoscopy (group 1), whereas eight neonates underwent a VP shunt placement (group 2). Nonsignificant difference between the groups was found concerning days after neuroendoscopy, clot extraction, third ventriculostomy, lamina terminalis fenestration, and septum pellucidum fenestration. In group 2, there was shunt dysfunction in five cases with shunt replacement in four cases. NEL is a feasible technique to remove intraventricular blood degradation products and residual hematoma in neonates suffering from posthemorrhagic hydrocephalus. In our series, endoscopic third ventriculostomy (ETV) + NEL could be effective in avoiding hydrocephalus after hemorrhage (no control group studied). Furthermore, patients without the necessity of VP-shunt had a better GMFCS in comparison with shunted patients.

Maternal-neonatal events resulting from medications for preventing hypertensive disorders in high-risk pregnant women: A systematic review and network meta-analysis.

There have been few studies reporting on maternal and neonatal events in high-risk pregnant women receiving medications for preventing hypertensive disorders of pregnancy (HDP). To identify placental abruption, postpartum hemorrhage, neonatal intraventricular hemorrhage, and neonates with small for gestational age (SGA) or growth restriction resulting from medications for preventing HDP in high-risk pregnant women using a network meta-analysis. All randomized controlled trials comparing the most commonly used medications (antiplatelet agents, anticoagulants, antioxidants, nitric oxide, and calcium) for preventing HDP in high-risk pregnant women were searched from the Cochrane Pregnancy and Childbirth's Specialized Register of Controlled Trials until July 31, 2020, without language restriction. Two of the authors independently selected the eligible trials. Two authors independently extracted the data and assessed the methodological quality of the included trials. Pairwise and network meta-analyses were used to determine comparative risk ratios and 95% confidence intervals. The 51 included trials involved 69 669 pregnant women. Compared with placebo/no treatment, antioxidants slightly reduced placental abruption with high-certainty evidence. Antiplatelet agents probably reduced SGA with low-certainty evidence and slightly increased neonatal intraventricular hemorrhage with moderate-certainty evidence. Antiplatelet agents probably reduce SGA, but neonatal intraventricular hemorrhage should be monitored. PROSPERO, CRD42018096276.

Innate immune activation and white matter injury in a rat model of neonatal intraventricular hemorrhage are dependent on developmental stage

BackgroundInflammation and white matter injury are consequences of neonatal intraventricular hemorrhage (IVH). Both white matter and the neuroimmune system are developing during the time which IVH occurs and its consequences develop. IVH has been studied in many different animal models; however, the effects of IVH occurring at different developmental time points in the same model have not been examined. Understanding how the timing of IVH affects outcome may provide important insights into both IVH pathophysiology and innate immune development. MethodsWe used intraventricular injection of lysed whole blood to model neonatal IVH in postnatal day (P)2 and P5 rats. Flow cytometry was used to detect innate immune activation. MRI was used to screen animals for the development of increased ventricular size. Immunohistochemistry for myelin basic protein was used to quantify white matter and corpus callosum thickness. ResultsP5 animals exhibited significant increases in several measures of classically pro-inflammatory innate immune activation that P2 animals did not. Animals with IVH induced at P5 also developed ventricular enlargement visible on MRI whereas animals with IVH induced at P2 did not. On histological analysis, there were no significant effects of IVH in P2 animals, but IVH in P5 animals reduced white matter labeling and corpus callosum thickness. ConclusionsIVH induces a strong innate inflammatory response in P5 as well as changes in ventricular size and reduction of white matter. P2 animals do not exhibit significant changes in innate immune activation or white matter structure after IVH. This suggests that white matter pathology from IVH is due in part to innate immune activation; and that the developmental stage of the innate immune system is a key determinant of IVH pathology.

Neonatal Intraventricular Hemorrhage Presenting as Pyrexia of Newborn: A Case Report

Abstract: &#x0D; Background Temperature instability is a relatively common presenting symptom in a Neonatal Intensive Care Unit (NICU) with sepsis being one of the major etiologies that need to be ruled out. However, an important differential diagnosis is a central fever. Many cases of Intracranial Hemorrhage/Intraventricular Hemorrhage (ICH/IVH) present with temperature dysregulation with no other clear associated symptoms, and cranial imaging for early identification and treatment of ICH/IVH is crucial. &#x0D; Case report A 3-day-old male born at 33 weeks and four days of gestation who was admitted to the neonatal critical care unit due to prematurity and respiratory distress was noted to be febrile during the fourth hospital day. The septic screen was negative, and the patient continued to spike fever while on broad-spectrum antimicrobial treatment. Due to an unexplained drop in his hematocrit, cranial ultrasound was done, and grade III IVH was identified. The patient continued to improve clinically, but the exact etiology of his IVH was not identified. His fever resolved without interventions, and his IVH continued to decrease in size. Serial cranial imaging was done in NICU, and no neurosurgical interventions were warranted. He was referred to neurosurgery and neurology and followed in the infant’s high-risk clinic. &#x0D; Discussion Sepsis is the top of differentials when managing a newborn infant in NICU. However, we must always keep our minds open to other differentials, including central hyperthermia. Extreme prematurity is a major risk factor for ICH/IVH in the neonatal period; nonetheless, other risk factors are identified, and many cases of ICH/IVH had no identified causative factor or even risk factors. &#x0D; Conclusion Identifying clinical presentation and risk factors associated with ICH and IVH in NICU patients is crucial for early diagnosis and offers appropriate management. A high index of suspicion is required to promptly diagnose ICH/IVH resulting in central fever and avoid unnecessary workup and treatment.