Replication of Genetic Associations in the Inflammation, Complement, and Coagulation Pathways With Intraventricular Hemorrhage in LBW Preterm Neonates

Background: Pathogenesis of intraventricular hemorrhage (IVH) in premature infants is multifactorial. Little is known about the influence of pro-inflammatory cytokine activation on the coagulation system in extremely preterm infants and its impact on the development of IVH. Objective: To determine the interaction between serum interleukin-6 (IL-6) and the coagulation system in preterm infants predisposed to the development of IVH. Methods: Vitamin K-dependent coagulation factors were examined retrospectively in 132 extremely preterm infants prior to vitamin K administration at the first day of life. Patients were grouped according to the occurrence of IVH and serum concentration of IL-6 >/<100 pg/ml. Results: Occurrence of IVH was associated with clinical diagnosis of chorioamnionitis, low gestational age, high CRIB score, air leak, catecholamine treatment, low initial hematocrit and increased serum concentration of IL-6. Infants developing IVH showed a diminished coagulation profile. Multivariable logistic regression analysis revealed decreased activity of coagulation factor VII, development of pneumothorax and low hematocrit as independent risk factors for the development of IVH. An increased IL-6 serum concentration was associated with a significantly decreased activity of coagulation factor VII and increased levels of fibrinogen. Conclusions: The association of elevated IL-6 levels with alterations of the coagulation profile and development of IVH found in our study supports the assumption of a close pathophysiological relation between inflammation and IVH.

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“…It is noteworthy that many of these studies focused on genes related to coagulation and inflammation [32,33]. …”

Section: Discussionmentioning

confidence: 99%

Elevated Interleukin-6 Concentration and Alterations of the Coagulation System Are Associated with the Development of Intraventricular Hemorrhage in Extremely Preterm Infants

Poralla¹,

Hertfelder

Oldenburg

et al. 2012

Neonatology

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“…There have been previous studies about gene-environment interactions with relation to IVH [7, 25-28]. In twin studies, the difference in the incidence of IVH in monozygotic and dizygotic twins was not statistically significant [7].…”

Section: Discussionmentioning

confidence: 99%

“…In twin studies, the difference in the incidence of IVH in monozygotic and dizygotic twins was not statistically significant [7]. The study by Ryckman et al [28] suggested that the heterozygous Leiden mutation (RS6025) in coagulation factor V (F5) was associated with an increased risk of developing IVH grade I or II [28, 29]. A study performed in Germany demonstrated genetic predisposition in the protein C anticoagulant pathway in 66% of children with congenital porencephaly [29].…”

Section: Discussionmentioning

confidence: 99%

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

Prasun¹,

Madan²,

Puthuraya³

et al. 2018

Dev Neurosci

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Background: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. Methods: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). Results: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). Conclusion: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.

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“…A study by Ryckman et al [24] included 271 very low birth weight infants born before 32 weeks of gestation. Ten genes potentially linked to increased IVH risk were isolated and examined, with specific single nucleotide polymorphisms selected for these candidate genes, based on previous research.…”

Section: Interleukin-1 (Il-1)mentioning

confidence: 99%

Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns

et al. 2016

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Proinflammatory cytokines are essential mediators and indicators of an inflammatory process occurring in the body. Their physiological role is to stimulate the immune response, yet their excessive propagation and interaction with cells outside the immune system may be linked to the risk of organ damage. This is specifically important in the case of immature tissues of fetuses and prematurely born infants. Analysis of the concentrations of specific cytokines in different compartments makes it possible to assess the risk of premature birth, preterm rupture of the membranes, and to determine an existing intrauterine infection. The purpose of this paper is to summarize the existing research concerning the relationships between the concentrations of specific proinflammatory cytokines in different compartments (maternal blood serum, amniotic fluid, umbilical cord blood, arterial and venous blood, and cerebrospinal fluid of the newborn) and the risk of intraventricular hemorrhage (IVH) and the degree of its severity. The paper takes also into account the assessment of the usefulness of cytokines as biomarkers for IVH and its complications (posthemorrhagic hydrocephalus, white matter injury).Keywords Intraventricular hemorrhage . Proinflammatory cytokines . Premature birth Dynamic development of perinatal medicine and neonatology has contributed to increased survival rates among prematurely born infants, leading at the same time to a relative increase in the number of multi-organ complications occurring in these babies. Intracranial, mainly intraventricular hemorrhages (IVHs), resulting from the immaturity of brain structures, represent one of the most common pathologies in premature infants. The incidence of this pathology is inversely proportional to gestational age. There are four degrees of IVH severity, graded I-IV [21]. Bleeding graded I and II is often self-limiting. Higher grade hemorrhages result in higher risk of neurodevelopmental delay; they are also the main cause of cerebral palsy and increased perinatal mortality rates in this group of infants [7,20]. It is estimated that IVH occurs in as much as 20% of infants born before 32nd week of gestation [4].The etiopathogenesis of IVH is complex. Besides gestational age (below 32 weeks) and body weight at birth (less than 1500 g), there are also other IVH risk factors identified, including absence of prenatal steroid therapy in women at risk of premature delivery, early clamping of the umbilical cord (less than 30 s after birth), symptoms of intrauterine infection in the mother and the newborn, and labor and delivery complicated by bleeding or perinatal hypoxia. The group of infants with an elevated IVH risk includes also newborns with intrauterine growth retardation or those who in the first days of their life were treated with crystalloids (bolus 10-15 ml/kg) and/or catecholamins for hypotension and NaHCO 3 for acidosis. IVH risk group includes also newborns with blood clotting disorders, thrombocytopenia, hypoglycemia, pneumothorax, lung bleeding, and...

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Replication of Genetic Associations in the Inflammation, Complement, and Coagulation Pathways With Intraventricular Hemorrhage in LBW Preterm Neonates

Cited by 37 publications

References 40 publications

Elevated Interleukin-6 Concentration and Alterations of the Coagulation System Are Associated with the Development of Intraventricular Hemorrhage in Extremely Preterm Infants

Elevated Interleukin-6 Concentration and Alterations of the Coagulation System Are Associated with the Development of Intraventricular Hemorrhage in Extremely Preterm Infants

Can Functional Polymorphisms in <b><i>VEGF</i></b> and <b><i>MMP</i></b> Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns

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