Hemorrhage In Preterm Infants Research Articles

Intraventricular Hemorrhage in Premature Infants: A Review of Risk Factors, Pathology, Treatment, and Prognosis

Abstract Intraventricular hemorrhage (IVH) in newborns is defined as bleeding within the ventricles, surrounded by the brain. This condition is most commonly observed in premature newborns and is directly proportional to gestational age; the smaller the gestational age, the higher the risk of IVH. It typically occurs in the subependymal germinal matrix, a highly vascularized area undergoing significant development in newborns and regression in full-term infants. The etiology is multifactorial and primarily attributed to the intrinsic fragility of the vascularization of the germinal matrix. Risk factors for IVH in premature infants include the immaturity of the cerebral vascular system, fluctuations in blood pressure, hypoxia, and oxidative stress. Furthermore, clinical factors such as respiratory distress syndrome, mechanical ventilation, and coagulation disorders contribute to the vulnerability of preterm infants to this complication. Regarding treatment, interventions can range from careful monitoring and medical support to surgical procedures such as cerebrospinal fluid drainage or ventriculoperitoneal shunting in severe cases. Pharmacological therapy, including the use of anti-inflammatory drugs, may be implemented to minimize brain injuries. Complications of IVH include obstructive hydrocephalus, non-obstructive hydrocephalus, post-hemorrhagic hydrocephalus, developmental disorders, cerebral palsy, and seizures. In conclusion, IVH in premature infants remains a complex and delicate issue in neonatology. An integrated approach covering both prevention and treatment is essential to minimize the negative impact of this complication on the neurological development of premature infants. Continuous research is necessary to develop innovative and effective strategies for managing this critical problem in neonatal medicine. Transfontanelar ultrasound remains the election method for diagnosis. Mild and moderate forms have shown favorable progression, while severe IVH has led to the development of post-hemorrhagic obstructive hydrocephalus.

Navigating the Complexities of Intraventricular Hemorrhage in Preterm Infants: An Updated Review.

Intraventricular hemorrhage (IVH) is a type of bleeding that occurs in the ventricular cavity of the brain. In this comprehensive study, we providea summary of the pathogenesis, diagnosis, and treatment of intraventricular hemorrhage in premature infants. Preterm babies are at high risk of developing IVH because their germinal matrix is not fully developed, making their blood vessels more prone to rupture. However, that is not necessarily the case in all preterm babies as the inherent structure of the germinal matrixmakes it more susceptible to hemorrhage. Incidences of IVH are discussed based on recent data which states that around 12,000 premature infants in the United States experience IVH each year. Although grades I and II make up the majority of IVH cases and are frequently asymptomatic, IVH remains a significant issue for premature infants in neonatal intensive care facilities worldwide. Grades I and II have been linked to mutations in the type IV procollagen gene, COL4A1, as well as prothrombin G20210A and factor V Leiden mutations. Intraventricular hemorrhagecan be detected using brain imaging in the first seven to 14 days following delivery. This review also shines a light on reliable methods for identifying IVH in premature newborns like cranial ultrasound and magnetic resonance imaging along with the treatment of IVH which is primarily supportive and involves the management of intracranial pressure, the correction of coagulation abnormalities, and the prevention of seizures.

Neuroimaging of Germinal Matrix and Intraventricular Hemorrhage in Premature Infants.

Germinal matrix and intraventricular hemorrhage (GM-IVH) are the major causes of intracranial hemorrhage in premature infants. Cranial ultrasound (cUS) is the imaging modality of choice for diagnosing and classifying GM-IVH. Magnetic resonance imaging (MRI), usually performed at term-equivalent age, is more sensitive than cUS in identifying hemorrhage in the brain. Post-hemorrhagic ventricular dilatation is a significant complication of GM-IVH and correlates with adverse neurodevelopmental outcomes. In this review, we discuss the various imaging findings of GM-IVH in premature infants, focusing on the role of cUS and MRI.

Evaluation of Chemokine CCL18 Level in Cord and Peripheral Blood as a Predictor of Intraventricular Hemorrhage in Preterm Infants

Evaluation of Chemokine CCL18 Level in Cord and Peripheral Blood as a Predictor of Intraventricular Hemorrhage in Preterm Infants

Temporary Surgical Management of Intraventricular Hemorrhage in Premature Infants.

Post-hemorrhagic hydrocephalus (PHH) in preterm infant is common, life-threatening and the main cause of bad developmental outcomes. Ventriculoperitoneal (VP) shunt is used as the ultimate treatment for PHH. Low birth weight and low gestational age are the combination of worse prognostic factors while the single most important prognostic factor of VP shunting is age. Aggressive and early intervention have better effect in intraventricular hemorrhage and intracranial pressures control. It reduces infection rate and brain damage resulted in delayed shunt insertion. It is extremely important to let PHH infants get older and gain weight to have internal organs to be matured before undergoing VP shunt. As premature infants undergo shunt after further growth, shunt-related complications would be reduced. So temporary surgical intervention is critical for PHH infants to have them enough time until permanently shunted.

The effectiveness of interventions to prevent intraventricular haemorrhage in premature infants: A systematic review and network meta-analysis.

Intraventricular haemorrhage (IVH) is a common problem in preterm infants, being a major cause of morbidity and mortality. Despite many randomised controlled trials comparing interventions to prevent IVH, the best prevention remains unclear. This study aims to review all the interventions which intended to reduce the incidence of IVH and compare them in a network meta-analysis. A search on MEDLINE, EMBASE, Emcare, and CENTRAL was performed. Randomised controlled trials which evaluated neonatal interventions with a primary aim to reduce incidence of IVH in preterm infants were eligible. A surface under a cumulative ranking curve (SUCRA) was produced to indicate the intervention's likelihood of being the most effective for preventing IVH. 40 studies were eligible, enrolling over 6760 infants. Twelve intervention groups were found, including delayed cord clamping, erythropoietin, ethamsylate, fresh frozen plasma, heparin, ibuprofen, indomethacin, magnesium, nursing interventions, sedation, tranexamic acid, and vitamin E. Vitamin E and indomethacin had the highest probability of being the best interventions to prevent IVH in premature infants, but interpretation of these results is difficult due to study limitations. Despite the impact of IVH, we were unable to identify a clearly beneficial treatment to reduce its incidence. Interpretation of the network meta-analysis was limited due to differences within studied populations, wide range of therapies trialled, and underlying advances in neonatal care between units, and over time. Although vitamin E and indomethacin appear to be promising candidates, contemporaneous trials of these, or novel agents, enrolling the most at-risk infants is needed urgently.

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants.

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

Perspectives : Understanding the Pathophysiology of Intraventricular Hemorrhage in Preterm Infants and Considering of the Future Direction for Treatment.

Remarkable advances in neonatal care have significantly improved the survival of extremely low birth weight infants in recent years. However, intraventricular hemorrhage (IVH) continues to be a major complication in preterm infants, leading to a high incidence of cerebral palsy and cognitive impairment. IVH is primarily caused by disruption of the fragile vascular network of the subependymal germinal matrix, and subsequent ventricular dilatation adversely affects the developing infant brain. Based on recent research, periventricular white matter injury is caused not only by ischemia and morphological distortion due to ventricular dilatation but also by free iron and inflammatory cytokines derived from hematoma and its lysates. The current guidelines for the treatment of posthemorrhagic hydrocephalus (PHH) in preterm infants do not provide strong recommendations, but initiating treatment intervention based on ultrasound measurement values before the appearance of clinical symptoms of PHH has been proposed. Moreover, in the past decade, therapeutic interventions that actively remove hematomas and lysates have been introduced. The era is moving beyond cerebrospinal fluid shunt toward therapeutic goals aimed at improving neurodevelopmental outcomes.

Hemangioma-related gene polymorphisms in the pathogenesis of intraventricular hemorrhage in preterm infants

PurposeThe aim of this study was to evaluate the possible relationship between four single nucleotide polymorphisms of hemangioma-linked genes encoding for anthrax toxin receptor 1 (ANTXR1 G976A), R kinase insert domain receptor (KDR T1444C), adrenoceptor beta 2 (ADRB C79CG), and insulin-like growth factor 1 receptor (IGF-1R G3174A) and the occurrence of IVH in a population of preterm infants.MethodsThe study includes a population of 105 infants born from 24 + 0 to 32 + 0 weeks of gestation and hospitalized at the Department of Neonatology (III level hospital) of Poznan University of Medical Science. Intraventricular hemorrhage was diagnosed with the use of cranial ultrasound. The classification of intraventricular bleeding was based on the Papile IVH classification.ResultsThe incidence of IVH was higher in infants with lower birth weight, lower APGAR scores, and low birth weight. The study revealed that IVH was approximately two times less likely to occur in infants with the allele G of IGF-1R 3174G > A.ConclusionIdentifying susceptible premature infants through genetic analysis could be a potential way to alleviate severe IVH and its subsequent consequences. Further research examining a wider range of relevant gene polymorphisms could help highlight any genetic patterns in this deleterious bleeding complication.

Risk factor analyses for intraventricular hemorrhage in preterm infants: A retrospective cohort study.

Very-low-birthweight (VLBW) infants can experience severe intraventricular hemorrhage (IVH) that can lead to life-long disability by impairing neurodevelopment. The aim of this study was to identify the risk and protective factors for severe IVH in VLBW infants. A retrospective, cross-sectional review of VLBW infants born at 22-28 weeks' gestation between January 2003 and December 2012 and listed in the Database of Neonatal Research Network in Japan was performed using a statistical model incorporating an odds ratio (OR) and medical center variation as a center variance ratio (CVR). A two-dimensional analysis using a combination of OR and the CVR described evolving measures of a clinical trial (for OR > 1) and standardization (for CVR > 1) concerning a factor of interest. The noteworthy significant protective factors were antenatal steroids (ANS) with and without premature rupture of membrane (OR: 0.43, CVR: 1.08, and OR: 0.68, CVR: 1.14, respectively) and the number of neonatal beds (OR: 0.94, CVR: 0.99) and staff nurses per neonatal bed (OR: 0.89, CVR: 0.99). Active promotion of ANS administration and consolidation of perinatal medical centers can mitigate the development of severe IVH in VLBW infants.

Neonatal and Obstetric Risk Factors of Intracranial Haemorrhage in Preterm Infants

Neonatal and Obstetric Risk Factors of Intracranial Haemorrhage in Preterm Infants

Use of Red Cell Indices for Screening of Hereditary Spherocytosis in Neonates: A Report of Two Cases Confirmed by Exome Sequencing

Prolonged unconjugated hyperbilirubinaemia is defined as neonatal jaundice persisting beyond 14 days of life. Hereditary Spherocytosis (HS) often remains underdiagnosed and is a notable cause of prolonged neonatal jaundice. Coombs negative haemolytic anaemias are an important cause of unconjugated hyperbilirubinaemia, and HS is one of the most common inherited red cell membrane disorders. Other causes of prolonged unconjugated jaundice include extravasated blood (cephalhaematoma, bruises, intraventricular haemorrhage in preterm infants), haemolysis (blood group incompatibility, red blood cell enzymopathies, and membranopathies), urinary tract infection, congenital hypothyroidism, and rare familial disorders such as Gilbert’s syndrome and Crigler-Najjar syndromes I and II. Herein, the authors present a case report of two male neonates (three week-old and 25dayold) who presented with hyperbilirubinaemia requiring intensive phototherapy, blood transfusion, an exchange transfusion, and were diagnosed with HS. A significant family history suggested haemolytic anaemia, and red cell indices, namely Mean Corpuscular Haemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), and the ratio of MCHC/MCV (neonatal HS index), helped suspect HS. Whole exome sequencing identified the specific mutation and confirmed the diagnosis of HS. Both of these neonates presented with prolonged neonatal jaundice, and HS was suspected based on the family history and red cell indices, namely MCHC and MCHC/MCV ratio, as highlighted in the present case series.

Etiology and Prognosis of Intracranial Hemorrhage in Premature Infants, Cohort Research

Etiology and Prognosis of Intracranial Hemorrhage in Premature Infants, Cohort Research

Interobserver reliability between pediatric radiologists and residents in ultrasound evaluation of intraventricular hemorrhage in premature infants.

Germinal matrix intraventricular hemorrhage (IVH) may contribute to significant morbidity and mortality in premature infants. Timely identification and grading of IVH affect decision-making and clinical outcomes. There is possibility of misinterpretation of the ultrasound appearances, and the interobserver variability has not been investigated between radiology resident and board-certified radiologist. To assess interobserver reliability between senior radiology residents performing bedside cranial ultrasound during on-call hours and pediatric radiologists. From June 2018 to June 2020, neonatal cranial ultrasound examinations were performed in neonatal intensive care unit. Ultrasound findings were recorded by the residents performing the ultrasound and the pediatric attending radiologists. In total, 200 neonates were included in the study, with a mean gestational age of 30.9 wk. Interobserver agreement for higher grade (Grade III & IV) IVH was excellent. There was substantial agreement for lower grade (Grade I & II) IVH. There is strong agreement between radiology residents and pediatric radiologists, which is higher for high grade IVHs.

Analysis of non-retinopathy of prematurity (ROP)-related fundus hemorrhage in preterm infants in China.

ObjectiveTo determine the incidence of fundus hemorrhage (FH) not associated with retinopathy of prematurity (ROP) during ocular screening and report their clinical features, risk factors, therapies, and prognosis in a large population of premature newborns.MethodsThe medical records of all preterm newborns admitted to the Department of Ophthalmology, Peking University People's Hospital, Beijing, from January 1, 2016 through August 31, 2021 were retrospectively reviewed. Fundus examinations were carried out by experienced retinal experts. Examination under anesthesia was carried out in newborns with abnormal fundus including vitreous hemorrhage (VH) or retinal hemorrhage (RH) >2 disks' diameter by a Retcam 2 system. A lens-preserving vitrectomy was performed in infants requiring a vitrectomy. A comprehensive medical history was also recorded and analyzed.ResultsDuring the 5-year period, a total of 7,260 preterm babies were screened. There were 82 (1.13%) newborns and 104 (0.72) eyes with FH, including VH or RH.Twelve (14.63%) newborns (16 eyes, 15.38%) had VH; 56 (68.29%) (74 eyes, 71.15%) had flame-shaped, superficial hemorrhages; six (7.31%) (6 eyes, 5.77%) had small, round, deep hemorrhages (<2 disk diameters in size); and eight (9.76%) (8 eyes, 7.69%) had large, round hemorrhages (>2 disk diameters). In all, there were 10 (12.20%) cases of intracranial hemorrhage. The mode of delivery was not found to be a significant factor in the occurrence of birth-related retinal hemorrhage (P = 0.22).Six newborns (eyes) with large, round retinal hemorrhage at the posterior pole while the macular was not impacted and 11 cases (15 eyes) with vitreous hemorrhage were required to receive close follow-up with average follow-up time of 105 days. A lens-sparing vitreous surgery was conducted in three patients without any complications.ConclusionPreterm newborns with FH that are not caused by ROP are more likely to have superficial, peripheral hemorrhages. Vaginal delivery compression and forceps may be associated with hemorrhage. A lens-preserving vitrectomy is required and considered safe for dense FH involving the refractive media.

Associations of variants of folate cycle genes with features of the clinical course of severe intraventricular hemorrhages in premature infants.

Summary data indicate that it has increased attention to the study of the role of the folate cycle and the genes encoding its key components in the complicated course of the neonatal period in premature infants. Therefore, the aim of our study was to investigate the relationship of folate cycle gene variants with the features of the neonatal course in premature infants with severe intraventricular hemorrhages (IVH). The study included 24 preterm infants with with IVHs of 3d and 4th degree that received standard clinical, laboratory and instrumental examination. Apgar scores at 1 and 5 minutes were significantly lower in patients with AA genotype according to variant A1298C of the MTHFR gene. The concentration of total protein on 6th day after birth was negatively correlated with the A66G variant of the MTRR gene. The mean concentration of ionized calcium in the first day after birth was higher in the subgroup of patients with the AA genotype (according to variant A1298C of the MTHFR gene). In the subgroup of patients requiring mechanical ventilation, the frequency of AA genotype according to variant A2756G of the MTR gene was significantly increased. The presence of respiratory disorders and oxygen dependence was negatively correlated with variant A1298C MTHFR. The day of surfactant administration was positively correlated with variant A1298C of the MTHFR gene. The results of this study indicate that gene variants MTHFR (C677T, A1298C), MTRR (A66G), MTR (A2756G), RFC1 (G80A) may affect the neonatal course in premature infants with severe IVH.

Intraventricular hemorrhage in extremely low birth weight infant: a case report

This article focuses on the problem of intraventricular hemorrhage in preterm infants with low and extremely low body weight. Premature newborns are most susceptible to this pathology due to the morpho-functional immaturity of brain tissues and blood vessels. Pathological factors lead to lesion of the vessel wall and a massive hemorrhage in the cavity of the ventricles, sometimes with a breakthrough into the white matter. The morphological findings of hemorrhage in the lateral ventricles of the brain in a child born with extremely low body weight are presented on an example of a clinical case. The article presents a description of the morphology of damage to the germinal matrix and choroid plexus as one of the most common sources of hemorrhage. The main attention is paid to the state of the blood vessels: arterioles, venules, capillaries. Possible causes and consequences of vascular injury in the periventricular region are indicated here. According to the recent studies, intraventricular hemorrhage appears more often due to damage to the choroid plexus in children born at 37 weeks of gestation and later. In this report we consider the problem of hemorrhage from the reducing germinal matrixs vessels into the subependymal region with spreading into the white matter and lateral ventricles.

Intraventricular hemorrhages in premature newborns: predictors of development

Intraventricular hemorrhage is the most common type of brain damage in infants with extremely low and very low body weight. The main source of intraventricular hemorrhages in premature infants are the vessels of the ventricular germinal zone, or germ matrix. Intraventricular hemorrhages are caused by many risk factors. The current concept is that predictors of development are classified into ante-, intra- and postnatal. The most significant among them is intrauterine infection, which can have a direct and indirect effect on the immature structures of the fetal brain. Also of great importance are the concomitant pathology of the cardiovascular system in the mother and complications of pregnancy and childbirth (placental abruption, rapid delivery, chronic placental insufficiency). On the part of the newborn, coagulation disorders in combination with immaturity of the hemostatic system, as well as pathology of the cardiovascular and respiratory systems are important. Predictors of intraventricular hemorrhages in premature infants (genetic, hemostasiological, morphological), require further study, analysis, and optimization of application in order to prevent and reduce the incidence of intraventricular hemorrhages.

Intraventricular haemorrhage in premature infants. Review of diagnostic methods, treatment and influence on neurodevelopment

Introduction: Preterm infants are at high risk for various neurological complications and mortality caused by hypoxemia, haemorrhage or inflammation concerning preterm delivery. Resulting brain lesions are mostly asymptomatic - they cannot be diagnosed clinically as such neuroimaging of preterm infants has become part of routine clinical care.&#x0D; In this article, newest studies about intraventricular haemorrhage, its complications and treatment methods were reviewed. The PubMed database was searched using keywords “intraventricular haemorrhage”, “preterm infant”, “intraventricular haemorrhage treatment”, “intraventricular haemorrhage outcome”. &#x0D; State of knowledge: Early diagnosis, appropriate nursing care and treatment can minimise morbidity. Prognosis is mainly determined by the severity of bleeding, occurred complications and neurological irreversible changes. Intraventricular haemorrhage can cause posthemorrhagic hydrocephalus, cerebral palsy, disability and mental retardation in further life. Even mild grades of haemorrhage can result in developmental disorders. Long-term issues such as neurodevelopmental disorders and cerebral palsy are as important as short-term problems. Detection of injuries affecting preterm infants is used to identify complications that might necessitate an intervention. While head ultrasound is the standard of care for routine neuroimaging screening, the use of brain magnetic resonance imaging has expanded recently.&#x0D; Conclusions: Considerable advances in neonatal care have resulted in improved survival and prognosis of development of preterm infants with intraventricular haemorrhage. Although there is a wide range of treatment methods, further studies are needed to assess their safety, effectiveness and impact on short- and long-term outcome.

Temporal trends in intraventricular hemorrhage in preterm infants: A Brazilian multicenter cohort

Intraventricular hemorrhage (IVH) is a serious problem in preterm infants. Brazilian national data are unknown. To evaluate the incidence and temporal trend of IVH in very low birth weight (VLBW) preterm infants of 18 centers of the Brazilian Network on Neonatal Research. National prospective multicenter cohort study including inborn VLBW preterm infants aged 230/7- 336/7 weeks' gestation, admitted between 2013 and 2018. The center with the mean incidence rate was used as reference. We applied two adjustments models using perinatal variables, and perinatal+neonatal diseases. Of 6,420 infants, 1951/30.4% (range 27.1-33.8%) had IVH and the disease showed a significant trend towards an overall increase in incidence over time (p=0.003), especially in three centers. Severe IVH (grade III or IV) occurred in 32.2% (range 29.2-34.5%) of those affected by IVH, with a stable incidence. After adjustments for perinatal variables, the differences persisted among centers: for global IVH, 7 centers had significantly lower rates (OR ranging from 0.31 to 0.62), and 2 presented rates higher than the reference center (OR ranging from 2.00 to 12.46) for severe HIV. Considering perinatal and neonatal variables, 6 centers had significantly lower rates (OR ranging from 0.36 to 0.60) for global IVH than the reference center and 3 had statistically higher rates (OR 1.72, 1.86 and 11.78) for severe forms. The incidence rate of IVH in this Brazilian cohort was high and it revealed an increasing trend towards over time. The severe IVH rate was also worrisome.