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

Poralla, Christine; Hertfelder, Hans‐Jörg; Oldenburg, Johannes; Müller, Annekatrin; Bartmann, Peter; Heep, Axel

doi:10.1159/000341266

Cited by 32 publications

(29 citation statements)

References 66 publications

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“…IL6 crosses the blood–brain barrier 39 and has procoagulative properties. 40,41 In addition, IL6 activation decreases vitamin K-dependent coagulation factors and subsequent IVH development. 40 Neurodevelopmental complications among infants who experience IVH are lessened if they received breast milk.…”

Section: Discussionmentioning

confidence: 99%

“…40,41 In addition, IL6 activation decreases vitamin K-dependent coagulation factors and subsequent IVH development. 40 Neurodevelopmental complications among infants who experience IVH are lessened if they received breast milk. 42 When adequate amounts of IL6 are present in breast milk, infants may receive exogenous coagulative protection against IVH, and neuroprotection to infants who had IVH may last into childhood.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Promoter Polymorphisms on Cytokine Concentration in Preterm Breast Milk and Subsequent Infant Outcomes

et al. 2016

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Background Breast milk concentrations of immune components are variable between women and interleukin (IL) differences may be associated with infant outcomes. Molecular mechanisms for milk variability remain unknown. Objective The aims were to (1) examine the relationship between maternal IL genotypes and milk concentrations of IL4, IL6, and IL10, (2) describe the trajectories of milk IL change, (3) examine whether maternal IL genotypes predict IL trajectories and/or average weekly IL concentration, and (4) examine if weekly IL levels and/or IL trajectories are associated with infant outcomes. Methods Milk aliquots were collected from each feeding of mother's own milk and pooled weekly. DNA was extracted from 1 sample of each mother's breast milk whey (n = 64), and single nucleotide polymorphisms (SNPs) of IL genes were genotyped. Milk IL concentrations were measured and trajectory analysis examined IL milk change over time. Multivariate breast milk IL concentration analyses controlled for gestational age and prepregnancy body mass index. Multivariate infant outcome (n = 73) analyses controlled for gestational age and the ratio of human milk to total milk. Results Trajectory analysis resulted in linear group shapes, with 2 distinct subgroups in IL6 and 3 subgroups in IL4 and IL10. Trajectory groups trended toward significance with calprotectin, intraventricular hemorrhage, and blood transfusions. Multivariate analyses resulted in trending associations between maternal SNPs and subsequent IL6 and IL10 milk levels. There was a trending relationship between IL milk levels and both fecal calprotectin and intraventricular hemorrhage. Conclusion Maternal IL SNPs may affect IL breast milk levels and IL milk levels may be associated with infant outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Promoter Polymorphisms on Cytokine Concentration in Preterm Breast Milk and Subsequent Infant Outcomes

et al. 2016

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“…The precise molecular mechanisms underlying the observed prolongation of coagulation tests in extremely premature infants' remains poorly understood [23,24]. Future ex vivo studies are required to elucidate the overall balance of procoagulant and anticoagulant pathways in this population, as plasma clotting time prolongation may not directly correlate with in vivo bleeding tendency.…”

Section: Discussionmentioning

confidence: 99%

Laboratory Coagulation Parameters in Extremely Premature Infants Born Earlier than 27 Gestational Weeks upon Admission to a Neonatal Intensive Care Unit

Neary¹,

Okafor²,

Al-Awaysheh³

et al. 2013

Neonatology

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Background: Few published data exist to guide interpretation of coagulation times in extremely premature infants. Objective: To determine coagulation reference ranges on day 1 of life in extremely premature infants. Methods: A retrospective review of day 1 coagulation tests was performed in 144 infants <27 weeks' gestation between 2004 and 2010 in a tertiary neonatal unit. Samples were drawn through a non-heparinized umbilical or peripheral venous catheter as part of routine clinical care. Results: Mean (SD) and median (range) prothrombin times (PT) of 21.5 (5.3) and 20.2 (13.3-39) s, respectively, activated partial thromboplastin times (APTT) of 75.2 (27.8) and 67.4 (34.9-191.6) s, respectively, and plasma fibrinogen levels of 1.9 (1.1) and 1.4 (0.5-4.8) g/l, respectively, were reported. Using reference intervals derived from the 2.5th to 97.5th centiles, ranges of 14.4-36.7 s, 40.5-158.5 s and 0.7-4.8 g/l were determined for PT, APTT and plasma fibrinogen levels, respectively. In a subcohort with grade 0-2 intraventricular haemorrhage (n = 92), mean PT and APTT were 20.9 and 71.3 s, respectively, versus mean PT and APTT of 23.1 and 88.4 s (p = 0.06 and p = 0.03), respectively for those with grade 3-4 intraventricular haemorrhage. Mean PT and APTT in a cohort of infants defined to be small for gestational age were 22 and 76.8 s. These results did not differ significantly from non-small for gestational age infants, with a mean PT and APTT of 19.5 and 73.4 s (p = 0.09 and p = 0.7). Conclusions: Reference ranges based on retrospective data were determined for PT, APTT and fibrinogen in a large cohort of extremely preterm infants.

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“…It usually develops during the first week of life, with about 75% of the cases occurring within the first 72 hours and 90% being diagnosed by the end of the first postnatal week [3, 4]. Predisposing risk factors include early gestational age, low birth weight, infection, inflammation and respiratory distress [5, 6]. IVH has neurological and developmental sequelae that include injuries to the white matter, hydrocephalus, poor motor and cognitive development, cerebral palsy and poor executive function [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Urinary Allantoin Is Elevated in Severe Intraventricular Hemorrhage in the Preterm Newborn

Esiaba

Angeles

Holden

et al. 2015

Transl. Stroke Res.

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Background Germinal matrix intraventricular hemorrhage (IVH) is the most common type of intracranial hemorrhage observed in preterm neonates. It is a precursor of poor neurocognitive development, cerebral palsy and death. The pathophysiology is not well defined, but damage to the fragile germinal matrix vasculature may be due to free radicals generated during inflammation and as a consequence of ischemia followed by reperfusion. Assessment of the oxidative stress status in these infants is therefore important. Urinary allantoin concentration was measured in preterm neonates as a marker of oxidative stress associated with IVH. Study design Urine was collected from 44 preterm neonates at four time points between 24 and 72 hours of life (HOL) and the allantoin content was determined by gas chromatography mass spectrometry (GCMS). Records were retrospectively reviewed and the incidence and severity of IVH was categorized as follows: no IVH (n=24), mild (grade 1-2) IVH (n=13) and severe (grade 3-4) IVH (n=7). Results Neonates with severe IVH showed significantly elevated allantoin levels vs subjects with no IVH from 36 HOL (0.098±0.013µmol and 0.043±0.007µmol, respectively, p=.002). The allantoin concentration remained elevated even at 72 HOL (0.079±0.014µmol and 0.033±0.008µmol, respectively, p=.021). There were no significant differences in allantoin levels in the no IVH and mild IVH groups. IVH was diagnosed by head imaging on average at about 11th post-natal day. Conclusion Urinary allantoin levels were significantly elevated during the first 3 days of life in the neonates subsequently diagnosed with severe IVH, suggesting that oxidative stress might be a crucial factor in IVH pathogenesis. Further studies are needed to assess the usefulness of urinary allantoin in early identification of preterm infants at risk for or with severe IVH, and monitoring of the response to interventions designed to prevent or treat it.

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

Cited by 32 publications

References 66 publications

Effect of Promoter Polymorphisms on Cytokine Concentration in Preterm Breast Milk and Subsequent Infant Outcomes

Effect of Promoter Polymorphisms on Cytokine Concentration in Preterm Breast Milk and Subsequent Infant Outcomes

Laboratory Coagulation Parameters in Extremely Premature Infants Born Earlier than 27 Gestational Weeks upon Admission to a Neonatal Intensive Care Unit

Urinary Allantoin Is Elevated in Severe Intraventricular Hemorrhage in the Preterm Newborn

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