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

Abstract

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...

Maternal body mass index and risk of intraventricular hemorrhage in preterm infants

“…Pregnancies complicated by conditions associated with increased inflammation, such as chorioamnionitis, pPROM, and prolonged rupture of membranes (ROM), have been linked to an increased risk of IVH (21)(22)(23)(24). It has been suggested that pro-inflammatory cytokines, in particular, may play a role in the development of IVH (25)(26)(27). The etiopathogenesis of IVH is complex, but evidence suggests that inflammatory processes may play a significant role.…”

Mean Platelet Volume as a Marker of Intraventricular Hemorrhage in Very Premature Infants

“…Imperfect autoregulation of cerebral blood flow (CBF) (7) and increased serum level of interleukins (ILs: interlukin-1 beta, interlukin-6, interlukin-8, interlukin-18) and tumor necrosis factor-alpha were observed to be linked with severe IVH in extremely premature infants and are associated with neurodevelopmental disorders in this group (8)(9)(10)(11) Mean platelet volume (MPV) as an accessible predictive marker in thromboembolic events such as strokes and acute myocardial infarction in adults has already been studied (12)(13)(14). Destruction of platelets in the periphery increases the production of platelets by bone marrow that leads to an increase in the number of immature platelets in the circulatory system, thus leading to high MPV (14)(15)(16).…”

Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus

“…Although increased levels of TGF-β1 have been implicated in white matter injury in the setting of IVH and PHH, Heep et al [ 11 ] contrarily found no significant difference. A recent review by Szpecht et al [ 29 ] on the role of cytokines in the pathogenesis of IVH suggested an association between IL-1β, IL-6, IL-8, and TNF-α with increased risk of PHH [ 12 , 13 , 30 ].…”